Baxter Recalls All Heparin Vial Products

Baxter International Inc announced yesterday, Thursday 28th February, that it was recalling all remaining multi-dose and single-dose heparin sodium and HEP -LOCK heparin flush products now that alternative suppliers are able to meet national demand for them.

Heparin sodium is a vital ingredient in surgical and medical procedures that has been used throughout the US since the 1930s. It is injected into millions of Americans every year to stop potentially fatal blood clots in their veins, arteries and lung. The drug is made from the lining of pig intestines and most of it comes from China.

The announcement was in a statement released by the US Food and Drug Administration on behalf of the drug company.

This follows the recall in January of nine lots of Baxter's heparin sodium injection multi-dose vials as a precautionary measure after hundreds of patients had severe allergic reactions, and also four patients died, after receiving the product. The drug company also stopped making the product pending a fuller investigation.

The FDA has since admitted that a Chinese plant that supplied Baxter with the heparin active ingredient, which is made from pigs' intestines, was not inspected by the agency. The agency said it had confused the supplier with another similarly named Chinese supplier on its database that had already been approved.

The HEP-LOCK heparin flush (used to flush intravenous lines and equipment to prevent blood clots) and single dose heparin sodium vials were not recalled because they had not been linked to the adverse reactions and it was essential to keep supplies of this vital ingredient flowing until the demand could be met by an alternative source.

Baxter produces nearly half the US demand for heparin used in operating rooms, dialysis centers and other critical care areas. Pulling their products before an alternative source was found would have "created more risk to patients requiring heparin therapy than the increased potential for experiencing an adverse reaction", said the FDA.

The agency has concluded there is now sufficient capacity from other suppliers and has given Baxter the go ahead to recall its remaining heparin sodium injection and heparin flush products.

According to Sandra Kweder, deputy director of FDA's Center for Drug Evaluation and Research, the only Baxter products that are still on the market use heparin sourced from a different supplier. These products contain heparin in premixed IV solution bags and have not been associated with adverse events.

Exactly how the patients came to have allergic reactions to the affected products is still a mystery. The FDA has sent two officers to China where an initial investigation found problems linked to incomplete removal of impurities, plant conditions and management of waste.

According to the Washington Post, Michael Rogers, director of the FDA's field investigation division, said that while the agency was concerned about what the investigators observed at the plant, it was not linking these concerns to the adverse events associated with Baxter's products.

The full Baxter product recall now comprises:

• Heparin sodium injection 1000 units/mL 10mL and 30mL multi-dose vials.


• Heparin sodium injection 5000 units/mL 10mL multi-dose vials.


• Heparin sodium injection 10,000 units/mL 4mL multi-dose vials.


• Heparin sodium injection 1000 USP units/mL single-dose vials.


• Heparin sodium injection 5000 USP units/mL single-dose vials.


• Heparin sodium injection 10,000 USP units/mL single-dose vials.


• All preserved and preservative-free 10 USP units/mL and 100 USP units/mL vials of HEP-LOCK and HEP-LOCK U/P.

The recall excludes Baxter's bagged heparin pre-mix IV solutions of heparin sodium in 5 per cent dextrose injection and heparin sodium in 0.9 per cent sodium chloride injection, said the company.

President of Baxter's Medication Delivery business, Peter J Arduini said:

"We have assurance from the US Food and Drug Administration that there is an adequate supply in the market to meet the demand for these critical and lifesaving drugs."

"The safety and quality of our products is always our highest priority, and we will continue to collaborate with the FDA as we work to determine the cause of the increased rate of adverse reactions and resolve this issue," he added.

Increased Lung Cancer Risk Associated With Certain Vitamin Supplements

A recent study published in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine reports that vitamin supplements do not protect against lung cancer, and may in fact increase the risk of developing it.

Dr. Christopher G. Slatore of the University of Washington and colleagues performed the analysis by selecting a prospective cohort of 77,126 people between 50 and 76 years of age who were all in the Washington State VITAL (VITamins And Lifestyle) program. The researchers analyzed the rate of lung cancer development over four years and how it correlates with current and past vitamin usage, smoking, and other characteristics pertaining to demography and medical history.

Slatore writes, "Our study of supplemental multivitamins, vitamin C, vitamin E and folate did not show any evidence for a decreased risk of lung cancer." In addition, he notes that participants who increased intake of supplemental vitamin E had slightly higher risks of lung cancer.

From the 77,126 people, 521 developed lung cancer; this is in line with the expected rate for this low-risk group. However, those who did develop lung cancer had a slight significant association between lung cancer and supplemental vitamin E in addition to the typical associations with smoking history, family history, and age.

According to the model, a person taking 100 mg/day of vitamin E for ten years increases the risk of lung cancer by seven percent. This is like a 28 percent increase in risk for a 400 mg/day dose for ten years. Slatore notes that this increase in risk was largely confined to current smokers.

Since so many people currently or used to smoke and so many people take vitamin supplements, the study findings can benefit public health. "Future studies may focus on other components of fruits and vegetables that may explain the decreased risk [of cancer] that has been associated with fruits and vegetables," notes Dr. Slatore. "Meanwhile, our results should prompt clinicians to counsel patients that these supplements are unlikely to reduce the risk of lung cancer and may be detrimental."

An editorial in the same journal issue by Dr. Tim Byers of the University of Colorado School of Medicine suggests people want to easily take a pill instead of eating a healthy diet, and this is why they believe that vitamin supplements are healthy or relatively harmless.

However, "fruits contain not only vitamins but also many hundreds of other phytochemical compounds whose functions are not well understood," writes Byers. One study found a 20 percent increase in cancer risk among people who ate the least amount of fruit, and this has led to the World Cancer Research Fund and the American Cancer Society to recommend two fruit servings each day.

Two servings of fruit per day "would likely lead to a reduced risk for lung cancer, as well as reduced risk of several other cancers and cardiovascular disease," writes Dr. Byers. "However, any benefit to the population of smokers from increasing fruit intake to reduce cancer risk by 20 percent would be more than offset if even a small proportion of smokers decided to continue tobacco use in favor of such a diet change."

Eat Your Broccoli, Save Your Bladder

According to a recent report in the American Association for Cancer Research's journal Cancer Research, receiving a concentrated extract of freeze dried broccoli sprouts reduced the development of animal bladder tumors by more than half.

Researcher Yuesheng Zhang, the study's chief investigator, notes that the finding is in line with previous human epidemiological studies that have shown a relationship between eating cruciferous vegetables and reducing the risk of bladder cancer. Zhang remarks: "Although this is an animal study, it provides potent evidence that eating vegetables is beneficial in bladder cancer prevention."

It is strongly held that cruciferous vegetables are effective tissue protectors partly due to isothyiocyanates (ITCs) - phytochemicals with well-known cancer preventive traits. Cruciferous vegetables such as mature broccoli, cabbage, kale, and collard greens have ITCs. Zhang notes that the bladder is especially sensitive to these natural chemicals: "In our experiments, the broccoli sprout ITCs after oral administration were selectively delivered to the bladder tissues through urinary excretion."

Compared to mature broccoli, broccoli sprouts have about 30 times more ITCs. The extract of broccoli sprouts given to animals in the study contains about 600 times more ITCs than mature broccoli.

High doses of the extract were associated with the greatest protection against bladder cancer development. However, humans who are at an increased risk for the cancer and who seek to receive protective benefits from broccoli most likely would not have to consume copious amounts of broccoli sprouts.

"Epidemiologic studies have shown that dietary ITCs and cruciferous vegetable intake are inversely associated with bladder cancer risk in humans. It is possible that ITC doses much lower than those given to the rats in this study may be adequate for bladder cancer prevention," Zhang said.

The researchers studied five groups of rats in order to test if and how well the sprout concentrate prevents bladder tumors. One group was a control and received nothing, and a second was given only the broccoli extract. These two groups did not present any tumors nor toxicity from the broccoli extract.

Zhang and colleagues gave the remaining three groups a chemical, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water that stimulates bladder cancer development. Two of the three cancer groups received broccoli extracts two weeks prior to receiving the drinking water with the carcinogenic chemical.

Almost all (96%) of the rats who received only BBN developed an average of two tumors each. Of the rats who received a low dose of broccoli extract, 74% developed cancer - about 1.39 tumors on average.

A high dosage of extract was associated with the least amount of tumors - 38% of this group developed cancer and the average number of tumors per rat was 0.46. The tumors that did develop in these animals were small in size compared to the ones that developed in the other groups.

Peer-Reviewed Science Must Be The Source For Policy Decisions Regarding Drug Harm-Reduction

The authors of a Reflection and Reaction comment in the March issue of The Lancet Infectious Diseases take a hard line on some health policy research posted on the Internet, especially regarding evidence based drug harm reduction. In particular, they focus on a website posted as the Institute on Global Drug Policy (IGDP) which prevents itself as"an online open access journal," but also happens to be a part of the Drug Free America Foundation, a non-profit organization that supports "efforts to oppose policies based on the concept of harm reduction."According to the authors, politicians must beware the misleading intentions of sites such as this one to prevent making improperly informed decisions about health policy.

Harm-reduction programs attempt to address the issues related to illegal drugs by means other than total abstinence, such as needle exchanges. According to the authors, Drs Evan Wood, Julio Montaner, and Thomas Kerr, British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital, and Department of Medicine, University of British Columbia, Vancouver, Canada, there is indeed a formidable (and expanding) mass of evidence that these harm reduction measures are beneficial. However, groups such as IGDP have focused their efforts in agains this effort, including the above mentioned website, which claims to exist for the dissemination of "opinion essays."

The authors say that this has influenced Canada's health policy already: "The DFAF seems to have had some recent success with this approach. In an apparent effort to persuade Canada's Prime Minister Stephen Harper that his government should withdraw support from North America's first medically supervised injecting facility (SIF) in Vancouver, the website recently published a critique of the SIF...The website has also posted a range of articles against needle exchange and other evidence based harm reduction programmes. The conclusions of the needle exchange articles clearly contradict scientific consensus documents, such as a recent report by the US Institute of Medicine."

Since these IGDP articles were published online, Canada's new federal government announced a new anti-drug strategy that increases law enforement efforts while perhaps endangering the future of the Vancouver SIF. According to the authors, it is troubling that Canada's federal health minister recently publicly referred to the IGDP report while claiming there is "growing debate" about SIF, despite all studies in conventional scientific publications indicating multiple benefits with negligible negative effects.

The authors conclude, attempting to analyze the public popularity of such actions. "It remains to be seen whether what has been described as the Canadian federal government's new 'ideological' opposition to harm reduction will win them votes. Unlike in the USA, where surveys suggest the public supports the country's 'war on drugs', recent surveys in Canada suggest that the Canadian public is catching up to science when is comes to support for harm reduction programmes. Although the Canadian public may be gaining wisdom, advancing evidence-based public health will now require that politicians are able to tell the difference between valid peer-reviewed science and essays posted on the websites of lobby groups."

Dietitians Top 10 List For A Healthier You… What You Need To Know…

March is National Nutrition Month(R). As the organization bringing you National Nutrition Month(R), this year, Dietitians of Canada shines the spotlight on food and nutrition and offers their Top 10 List for a Healthier You. It's what Canadians need to know to take action to eating healthier, being more active and feeling great.

Confused about… what is a healthy weight for you? what is a portion size? how to read the Nutrition Facts panel on packaged food to make the best choice? or, which vegetables and fruits have the most antioxidants? The Dietitians Top 10 List can guide you down the road to good health.

"There's lots of advice in the market place and in the media about nutrition and health," says Mary Sue Waisman, registered dietitian and official spokesperson for DC's National Nutrition Month®. "When it comes to making wise food choices, get your advice from the most trusted source - a registered dietitian," adds Waisman. "Dietitians across Canada have weighed the evidence and identified 10 key steps to tune up Canadians' eating habits and reduce their risk of developing chronic diseases, added Ms. Waisman. "Take the Dietitians of Canada challenge for making 10 positive changes to eating and activity habits - at home, at school, at work and at play."

The goal this year is to help Canadians discover practical solutions to eat well and live well. Throughout March, dietitians in your community will be engaging people in healthy eating activities. Watch for grocery store tours to help consumers decipher nutrition labels and dietitians hosting discussions and providing presentations on how to help family members eat healthier.

Make National Nutrition Month® the time to get on the right track with healthy eating and active living. Start by making the Dietitians of Canada website http://www.dietitians.ca/eatwell your 'go to' place for trusted nutrition information and for fun and healthy eating ideas. Talk to a registered dietitian and together develop a personal plan that meets your needs, preferences and lifestyle. To find a registered dietitian in your area, visit http://www.dietitians.ca/find.

Dietitians of Canada's website offers a number of resources with practical food solutions to help consumers make healthier food choices. At http://www.dietitians.ca/eatwell, consumers can assess their food choices, based on Canada's Food Guide, through the interactive tool EATracker. It provides personalized feedback on the total intake of energy and essential nutrients and compares this to what is recommended for age, gender and activity level. Consumers can create a one-day menu with Let's Make a Meal! and analyze their favourite recipes with the Recipe Analyzer.

Dietitians of Canada represents and supports almost 6000 dietitians across Canada and has led the National Nutrition Month® Campaign for over 27 years.

Dietitians of Canada acknowledges its food industry partners who help to bring National Nutrition Month® messages to Canadians. This year's sponsors are: Eurest - Chartwells -Morrison members of Compass Group Canada, Dairy Farmers of Canada and General Mills Canada Corporation.

School Nutrition Experts Call For Child Nutrition Funding And Uniform Nutrition Standards

Early next month, more than 700 school nutrition professionals will discuss the crisis in funding for school meal programs and urge the Congress to require science-based, yet practical, uniform national school nutrition standards to govern the sale of all foods and beverages available during the school day. The School Nutrition Association's (SNA) 36th annual Legislative Action Conference in Washington, DC, March 2-5, 2008, will bring together school nutrition directors and supervisors, nutritionists, state child nutrition directors and foodservice industry representatives.

The emphasis on nutrition standards will build from efforts related to the drafting of the Farm Bill last year. This year however, as the national economic picture becomes more uncertain, school nutrition professionals will also provide lawmakers with the facts on school meal costs. The child nutrition programs are both under pressure to serve nutritious meals to more low-income children while being pinched by increased food, labor and milk costs.

"The federal government currently reimburses schools $2.47 for each balanced, healthy meal provided to children from families making 130% of poverty or less. A latte costs more. This is not adequate to cover the cost of producing a school meal," said Mary Hill SNS, president of SNA. The costs of food, transportation, labor and benefits, training, equipment and indirect expenses, are all increasing rapidly and meal charges as well as federal, state and local financial support for the child nutrition programs have not kept pace.

The key legislative issues the School Nutrition Association (SNA) is advocating for this year are:

- Giving the Secretary of Agriculture the authority to regulate and enforce the sale of food and beverages outside of the cafeteria.

- Requiring all a la carte and competitive food sales to be consistent with the Dietary Guidelines, as is required for school meals.

- Requiring national uniformity for the school meal pattern throughout the country. Children in all states and local districts need the same nutrients to grow and be healthy. The current lack of uniformity is increasing the cost of the programs.

- In the face of record food, labor and milk process, calling for adequate funding to support healthful meals being offered through school nutrition programs.

Activities of the 36th Annual Legislative Action Conference at the J.W. Marriot Hotel in Washington, DC will also include:

- Senate Agriculture, Nutrition and Forestry Committee Chair Tom Harkin (D-Iowa) and Ranking Member Saxby Chambliss (R-Ga.) as well as House Agriculture Committee Chair Colin Peterson (D-Minn.) Noted political commentator Amy Walter will give the opening keynote address.

- Panel discussions will include SNA's 2008 legislative priorities, perspectives on the need for national nutrition standards, the school nutrition funding crisis and an update on child nutrition activities from the USDA.

- SNA members will take their message to Capitol Hill, sharing the nutritional value of school meals and the need for key policy changes with members of Congress on March 4, 2007.

- On Tuesday, March 4, 2007, SNA president Mary Hill, SNS is scheduled to testify at a hearing held by the House Committee on Education and Labor.

- The Global Child Nutrition Foundation and SNA will honor the Executive Director of the Congressional Hunger Center Ed Cooney with the 2008 Gene White Lifetime Achievement Award at the "A Possible Dream Gala" on Tuesday evening, March 4, at the Ronald Reagan Building and International Trade Center. Other award recipients will be Geri Dee, SNS, 2007 Outstanding School Nutrition Director of the Year and Mimi Ford 2007 Individual Industry Member of the Year. Proceeds from the evening will benefit the Global Child Nutrition Foundation's initiatives to promote sustainable school feeding programs worldwide.

The School Nutrition Association is a national, non-profit professional organization representing more than 55,000 members who provide high-quality, low-cost meals to students across the country. The Association and its members are dedicated to feeding children safe and nutritious meals. SNA is the only association devoted exclusively to protecting and enhancing children's health and well being through school meals and sound nutrition education.

Wonderful Variety Of Pomegranate Juice Is The Leader In Healthy Beverages

A recent study published in the Journal of Agriculture and Food Chemistry found that pomegranate juice from the California-grown Wonderful variety of pomegranate is the leader in the healthy beverage category by demonstrating the most complete free radical scavenging activity, greater protection of LDL-cholesterol from oxidation, and the highest polyphenol content compared to red wine and several juices.

The study, led by Dr. David Heber at the Center for Human Nutrition, David Geffen School of Medicine, University of California Los Angeles, found that POM Wonderful 100% Pomegranate Juice tested higher in overall phenolic content and antioxidant activity than red wine and Concord grape, blueberry and orange juices. POM Wonderful 100% Pomegranate Juice even ranked higher than other beverages that have recently been touted as containing superior levels of antioxidants such as acai juice and white and green teas. Unlike all previous studies that only included one test against these other types of beverages, this Heber study conducted a series of seven tests on all the beverages, resulting in a novel and more accurate methodology.

"Often times, a beverage will make a claim about its superior antioxidant content based on the results of one test alone that provides the highest antioxidant capacity," said Dr. Heber. "What is important about this study is that all the beverages included were run against several tests resulting in a more complete assessment of a beverage's antioxidant activity and capability."

Results of the study showed that POM Wonderful 100% Pomegranate Juice had the greatest range of free radical fighting ability. The antioxidant potency composite index was at least 20% greater than any other beverage included in the study. To determine overall antioxidant content and functionality, each of the polyphenol-rich beverages included in the study were run against four tests for antioxidant potency.* In addition, all beverages were tested for their ability to inhibit LDL oxidation and evaluated for total polyphenol content.

POM Wonderful 100% Pomegranate Juice is the only pomegranate juice backed by $23 million in medical research. Over the last decade, 10 medical research studies have been published in peer-reviewed journals documenting the beneficial effects of POM Wonderful 100% Pomegranate Juice on human health, particularly in regards to heart disease, prostate cancer and erectile dysfunction. Through its proprietary juicing technology, POM Wonderful is the only company able to extract the full benefits of polyphenol antioxidants and guarantee its juice is 100% authentic pomegranate juice derived from its California-grown Wonderful variety of pomegranate.

For more information regarding the health benefits of POM Wonderful 100% Pomegranate Juice, visit http://www.pomegranatetruth.com/.

About POM Wonderful

POM Wonderful is the largest producer of California Wonderful pomegranates and the company exclusively grows and sells this variety. The company also juices its fresh pomegranates to make its delicious, all-natural, POM Wonderful Pomegranate Juice and POMx, a highly-concentrated, incredibly powerful blend of all-natural polyphenol antioxidants harnessed from the pomegranate by a patent-pending process. POMx is available exclusively in POM Tea, Light POM Tea, POMx Pills® and POMx Liquid. ® POM Wonderful Pomegranate Juice, POM Tea and Light POM Tea are available year-round at retail and are found in the refrigerated section of supermarkets and grocery stores nationwide. POMx Pills and POMx liquid are available at http://www.pompills.com/. To learn more, visit http://www.pomwonderful.com/.

* Antioxidant potency tests include Tolox equivalent antioxidant capacity (TEAC), total oxygen radical absorbance capacity (ORAC), free radical scavenging capacity by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP).

UNAIDS Welcomes United States Congressional Action To Renew Its Global AIDS Programme

The Joint United Nations Programme on HIV/AIDS welcomes the news that the United States House of Representatives Committee on Foreign Affairs has approved the "Tom Lantos and Henry J. Hyde Global Leadership on HIV/AIDS, Tuberculosis and Malaria Reauthorization Act of 2008." This action sends a strong signal that the United States is committed to maintaining its leadership role in the global response to AIDS.

UNAIDS also welcomes news that the reauthorization includes the key principles of promoting a truly global effort supported by bold new investments; moving from an "emergency" to a "sustainability" strategy; and maximizing effectiveness of investments through partnership and coordination.

Past and current investments are working. For example, more than 2.5 million people have access to HIV treatment with new encouraging data expected soon. HIV prevalence among young pregnant women (15-24) attending antenatal clinics has declined since 2000/2001 in 11 of the 15 most affected countries. New HIV infections can be prevented if the world remains committed to scaling up essential HIV prevention, treatment, care, and support efforts globally.

With more than 32 million people infected with HIV worldwide, the global commitment to AIDS has never been more important. UNAIDS is pleased with the bipartisan vote in the committee and hopes the US Congress maintains the momentum to move this legislation forward.

UNAIDS is an innovative joint venture of the United Nations, bringing together the efforts and resources of the UNAIDS Secretariat and ten UN system organizations in the AIDS response. The Secretariat headquarters is in Geneva, Switzerland-with staff on the ground in more than 80 countries. Coherent action on AIDS by the UN system is coordinated in countries through UN theme groups, and joint programmes on AIDS. UNAIDS' Cosponsors include UNHCR, UNICEF, WFP, UNDP, UNFPA, UNODC, ILO, UNESCO, WHO and the World Bank.

Mysteries Of Vitamin A Metabolism During Embryonic Development Unlocked By Rutgers Researchers

Researchers at Rutgers have unlocked some of the mysteries of how the developing embryo reacts to fluctuations in the amount of vitamin A present in the maternal blood stream. Their results are presented in the February 28 issue of the Journal of Biological Chemistry.

The researchers studied the role of LRAT, a protein that facilitates the formation of vitamin A stores in the body, during embryonic development. In particular, they showed how LRAT protects developing tissues from potentially toxic levels of vitamin A that have been ingested by the mother. Although this function of LRAT had previously been hypothesized in adults, this is the first time that its role has been demonstrated during embryonic development.

The developing mammalian embryo is entirely dependent on the maternal circulation for its supply of retinoids, the vitamin A metabolites produced in the body. These are essential nutrients and they control the formation of the embryo's heart, central nervous system, eyes and other important organs and tissues. Malformations of the developing embryo can occur when too little, or too much, vitamin A is consumed by the mother.

"We were looking for the mechanisms that allow the fetus to maintain adequate amount of retinoids, whether the mother has over- or under-consumed vitamin A," said Dr. Loredana Quadro, an assistant professor in the Department of Food Science and member of the Center for Lipid Research at the Rutgers School of Environmental and Biological Sciences. "We also looked at the effects of different levels of vitamin A being transferred from the mother to the fetus."

When vitamin A is ingested, it is converted into retinyl ester (RE) in the intestine from where it is secreted in the bloodstream packaged with other dietary lipids into lipoprotein particles called chylomicrons. The majority of dietary RE reaches the liver, the main body storage site of vitamin A. Under insufficient dietary vitamin A intake, the liver transforms RE into retinol (ROH), which is then secreted into the bloodstream bound to retinol-binding protein (RBP), its sole specific serum carrier, to be delivered to the target tissues. Upon intake through a specific membrane receptor named Stra6, ROH is ultimately converted to retinoic acid (RA), which is the active form of vitamin A. If tissue RA is in excess, it is transformed into inactive forms, such as 4-hydroxy retinoic acid or 4-oxo retinoic acid (OXO-RA) by the action of a specific enzyme named Cyp26A1.

"When we think about vitamin A, we think about one compound," said Quadro. "But in reality, the term vitamin A comprises a family of different compounds. Each one has a slightly different action, and plays a different role."

The Rutgers researchers took a closer look at how ROH is metabolized into RE and RA to maintain an optimal balance of retinoids during the formation of the embryo. Mutant mice lacking both RBP and LRAT were generated to perform this study, so as to interfere with the two main pathways of maternal vitamin A delivery to the fetus (ROH-RBP from the liver stores and RE of dietary origin).

"We hypothesized that the lack of ROH-RBP and LRAT would make the embryo more vulnerable to changes in maternal dietary vitamin A intake," said Quadro "and our data proved this to be correct. Indeed, a severe embryonic vitamin A deficiency is readily attainable when the mothers are deprived of dietary vitamin A during pregnancy. Therefore, this strain turned out to be a very good model to study how embryonic development is affected by fluctuations in the amount of retinoids present in the maternal diet and hence in the maternal circulation".

The researchers identified LRAT, Cyp26A1 and Stra6 as the three key molecular players that act in coordination to protect the developing tissues from potentially detrimental levels of vitamin A ingested by the mother. "Understanding vitamin A metabolism in the developing fetus could have broad implications," said Quadro. "Consumption of large doses of dietary supplements and vitamins, including vitamin A, has become a very common practice in recent years, generating the necessity to investigate the effects of high doses of vitamin A intake at different stages of the lifecycle, including pregnancy and development. These studies expand our knowledge of maternal-fetal nutrition and dietary contribution to embryonic development and may ultimately provide new insight into appropriate dietary practices during pregnancy."

This research was lead by Quadro and carried out primarily by her lab members, Youn-Kyung Kim, a graduate assistant, and Dr. Lesley Wassef, a post-doctoral associate. Others contributing to the study were Leora Hamberger, a former research assistant in Quadro's laboratory, Dr. William Blaner and Roseann Piantedosi from Columbia University and Dr. Krzysztof Palczewski from Case Western Reserve.

Efforts To Fix Or Kill Lung Cancer Cells Thwarted By Protein

A protein that helps lung cancer cells thrive appears to do so by blocking healthy cells' ability to fix themselves when radiation or chemicals, such as nicotine, damage their DNA, according to a University of Florida study to be published Friday (Feb. 29) in the journal Molecular Cell.

High levels of the protein, known as Bc12, are found in the cells of lung cancer patients who smoke.

Previous UF research has shown that nicotine activates the protein, which helps tumor cells live long past their natural lifespan and resist chemotherapy. The new findings explain how the protein enables cancer cells to circumvent the body's own efforts to change them back into healthy cells -- or evade treatments designed to kill them.

Cancer is frequently associated with the accumulation of genetic aberrations in cells' chromosomes. If these damaged cells can't access their built-in repair system and subsequently survive long enough to divide and multiply, they pass along their mutations.

"If a cell experiences DNA damage, often that DNA can be repaired. But we found that Bc12 can block the DNA repair mechanism, which promotes tumor formation and genetic instability," said Dr. Xingming Deng, an assistant professor in UF's College of Medicine who is affiliated with the UF Shands Cancer Center. "This is a very important fundamental mechanism that explains why this protein has (a cancer-forming) function."

Researchers say just one cell that develops a genetic mutation and is unable to repair itself could be enough for a full-blown tumor to develop.

"Lung cancer is the No. 1 killer of all cancer types; it is the most dangerous," Deng said. "We wanted to find a way to treat lung cancer, how to prevent lung cancer, because lung cancer prognosis is very poor."

Nearly 162,000 people will die from lung cancer in 2008, accounting for about 29 percent of all cancer deaths, according to the American Cancer Society. More people die of lung cancer than of colon, breast and prostate cancers combined.

In the study, UF scientists performed a series of laboratory experiments on lung cancer cells in culture that illuminated the molecular chain of events that allows Bc12 to disrupt DNA repair.

Deng also plans to explore the possibility that nicotine-induced activation of Bc12 can be blocked to increase chemotherapy's effectiveness.

"This will probably help us in the future find ways to prevent tumors," said Deng, adding that the protein could be a target for drug development. "We can target this mechanism and somehow find a way to prevent tumor formation."

he research was funded by about $1.2 million in grants from the National Institutes of Health and the Flight Attendant Medical Research Institute. FAMRI was established in 1997 as a result of a $300 million settlement between airline flight attendants and the tobacco industry. The nonprofit organization awards grants for research focusing on smoking-related illnesses.

Give Flu Shots To All Kids Says CDC Panel

A panel of experts that advises the US Centers for Disease Control and Prevention (CDC) recommends all American children over 6 months be vaccinated against seasonal flu, starting as soon as possible but perhaps more feasibly in the 2008-09 flu season because most doctors will have ordered all their flu shots for the current season.

The CDC does not have to follow the recommendation of its Advisory Committee on Immunization Practices but it usually does. The panel met yesterday, Wednesday 27th February, in Atlanta, Georgia, and voted unanimously in favour of the recommendation.

The current CDC recommendation is for vaccination of children between 6 months and 5 years old. This new recommendation, if adopted, will extend to all children between the age of 6 months and 18 years old.

This move adds about 30 million children to the flu vaccination list across the country, said CDC Curtis Allen to the press. Although there are nearly 60 million children aged 5 to 18 in the US, a lot of them are already covered under current recommendations, he said in a telephone interview with Reuters.

The CDC predicts the actual number that will get the vaccination will be around 7 million, based on current take up rates.

Between 5 and 20 per cent of the US population get the flu every year, and the disease kills about 36,000 people across the country every year, most of them elderly, but some healthy children too.

The 26 US states monitored by the CDC lost 68 children to the flu last year, half of whom were school age. 22 children have died so far this year, said the Los Angeles Times.

More than two thirds of Americans should have the flu shot every year, but most of them don't know this, said the CDC. This new recommendation makes it clear that all children should be vaccinated, said the panel.

According to a Bloomberg news report, pediatrics professor at Oklahoma State University, Stanley Grogg, told the panel just before it voted that the previous situation was too complicated, resulting in too many vulnerable unvaccinated children. It is much easier to remember a blanket recommendation for all children up to the age of 18, "than jumps along the way", he said.

It will not be mandatory for every child to have the flu shot, which is also available as a nasal spray, but the CDC's declaration will make it more likely that doctors will store and offer the vaccine.

Director of the CDC's National Center for Immunization and Respiratory Diseases, Dr Anne Schuchat, told the media:

"This new recommendation will help parents understand that all children can benefit from vaccination."

CDC approval means flu vaccinations will most likely be covered by insurance. The government insurance scheme for children, for example, covers about 45 per cent of American children, said the Los Angeles Times.

The CDC referred to a study on flu vaccination among children aged from 6 to 23 months that showed full vaccination (two shots) reduced hospital stays due to flu by around 75 per cent between 2005 to 2007, and partial vaccination (one shot) had a similar result.

Gary Stein of Families Fighting Flu, who lost his 4 year old daughter, Jessica, to the flu in 2002, spoke at the advisory meeting. He said afterwards they were "very pleased" with the panel's decision. He told Reuters that:

"Doctors follow these recommendations in advising their patients."

"Parents read it, and vaccination rates are so low that this awareness strongly follows the guidance," he added.

Health officials are hoping the new recommendation, if adopted, will also help to restore public confidence in flu vaccination. The flu shots this year have not been as good a match as usual to the types of flu viruses that are circulating. Out of the last 19 years, this has happened 3 times.

Corn Genome Unravelled

A group of scientists have completed a working draft of the genome sequence of corn, also known as maize, a widely grown crop that is vital to US agriculture. They hope the unravelling of this genome will speed up the development of better crop varieties to meet growing demand for food, animal feed and fuel.

The team, led by Dr Richard K Wilson, director of Washington University's Genome Sequencing Center in St Louis, Missouri, will reveal its work today, Thursday 28th February, at the 50th Annual Maize Genetics Conference in Washington, DC.

The draft includes about 95 per cent of the corn genome. Wilson and colleagues hope to complete the rest by the end of the year.

"Although it's still missing a few bits, the draft genome sequence is empowering," said Wilson.

"Virtually all the information is there, and while we may make some small modifications to the genetic sequence, we don't expect major changes," he added.

Maize, or corn, is an underlying foodstuff used in the manufacture of a wide variety of foods and other products, from the more familiar breakfast cereal to ethanol, shoe polish and toothpaste. It is also a vital food for cattle and other animals.

Wilson said that this first draft is "exciting" because:

"It's the first comprehensive glimpse at the blueprint for the corn plant."

"Scientists now will be able to accurately and efficiently probe the corn genome to find ways to improve breeding and subsequently increase crop yields and resistance to drought and disease," he added.

There are 2 billion DNA nucleotide bases in the corn genome, making it about the same size as the human genome. This is significantly larger than the rice genome which has about 430 million bases.

A DNA nucleotide base is a chemical building block of which there are four kinds, each represented by a letter: A for adenine, G for guanine, C for cytosine, and T for thymine.

The hardest part of the work Wilson and colleagues faced was to get the order of the bases right. About 80 per cent of the DNA sequence is repeated, and corn has 50,000 to 60,000 genes, about twice as many as humans. Many of these genes are mobile (transposons), making them much more difficult to "count" compared to the stationary ones.

Genes are large groups of nucleotide pairs that either code for a type of protein or cell component, or regulate the expression of other genes. An organism's complexity does not depend on the number of genes in its genome. And some genes have sequences in common with other genes. The concept of a gene is not fixed and still changing as scientists discover more about them.

Wilson explained that the task of sequencing the corn genome was:

"Like putting together a 1,000 piece jigsaw puzzle with lots of blue sky and blue water, with only a few small sailboats on the horizon."

"There were not a lot of landmarks to help us fit the pieces of the genome together," he added.

Other cereal crops could also benefit from this research, not just other varieties of corn, but also rice, wheat and barely, and other applications.

The research project, backed by the National Science Foundation (NSF), the US Department of Agriculture and the US Department of Energy, with a budget of nearly 30 million dollars, started in 2005.

NSF director Arden L Bement Jr stressed the importance of corn as "one of the most economically important crops for our nation".

"Completing this draft sequence of the corn genome constitutes a significant scientific advance and will foster growth of the agricultural community and the economy as a whole," he said.

The rest of the team includes scientists from the University of Arizona in Tucson, Cold Spring Harbor Laboratory in New York and Iowa State University.

Wilson and colleagues have been sharing the sequencing information they have unravelled through the online public DNA database, GenBank and maizesequence.org.

The precise variety of corn that Wilson and colleagues have been studying is called B73, which was developed at Iowa State University several decades ago. B73 is known for its high yield and is widely used for commercial breeding of corn and also for research.

Plant biologist Dr Ralph S. Quatrano, who is Spencer T Olin Professor and chair of Washington University's Department of Biology spoke of the range of applications of this discovery:

"The genome will help unravel the basic biology of corn. That information can be used to look for genes that make corn more nutritious or more efficient for ethanol production, for example."

The genome sequence of rice has already been unravelled, so sequencing a second grain crop will help scientists to find the genetic similarities and differences between them, said Quatrano.

Project collaborator Dr Rob Martienssen of Cold Spring Harbor Laboratory, was also enthusiastic about this:

"The maize genome sequence will be of great interest to maize geneticists and biologists around the world, but also will be an important resource for plant breeding and biotechnology companies."

"The maize sequence will be an invaluable reference for research, especially in renewable energy and biofuels, similar in significance to the human genome sequence for biomedical research," added Martienssen.

Over 40 per cent of the world's corn is produced in the US, where a record 13.1 billion bushels were grown in 2007, representing a 25 per cent increase on 2006, according to the US Department of Agriculture.

Antibiotic Resistant E. Coli Could Soon Become Prevalent, Similar To MRSA

It is possible that hospital types of antibiotic resistant Escherichia coli (E. coli) bacteria may soon infect patients in community settings. This would be a situation similar to that of community-acquired meticillin-resistant Staphylococcus aureus (MRSA), according to a Review published in March in The Lancet Infectious Diseases.

Often, these E. coli infections manifest themselves as urinary tract infections. Recent reports have also described antibiotic resistant E. coli strains in bloodstream infections. The authors of the report, Dr Johann Pitout, Calgary Laboratory Services, Calgary, and University of Calgary, Alberta, Canada and Dr Kevin Laupland, University of Calgary, Alberta, Canada, state that the antibiotic resistant E. coli bacteria that cause these infections should be identified soon to prevent their transmission and help select more effective antibiotics.

This Review focused on types of E. coli that produce β-lactamases -- these enzymes help give E. coli their antibiotic resistance. Notably, many surveys since 2000 from various European countries (including UK, Spain, Italy, Greece, and Canada) have shown a trend of resistance to various antibiotics in E. coli. According to the authors, "Infection control practitioners and clinicians need the clinical laboratory to rapidly identify and characterize different types of resistant bacteria efficiently to minimize the spread of these bacteria and help select more appropriate antibiotics...these bacteria have become widely prevalent in the community setting in certain areas of the world and they are most likely being imported into the hospital setting."

They recommend that funding be directed internationally to follow and monitor the propagation of these resistant E. coli in hospital and community settings. Their conclusion is that the risk of bloodstream infections in the community caused by this bacteria, while currently low, may in the future become a regular clinical problem, especially in the β-lactamase producing E. coli. These infections are currently rare, but it is possible that, in the near future, clinicians will be regularly confronted with hospital types of bacteria causing infections in patients from the community, a scenario very similar to that of community-acquired MRSA."

House Foreign Affairs Committee, White House Meet To Discuss Global AIDS Program Bill

House Foreign Affairs Committee members and White House officials met on Tuesday and agreed on a compromise draft bill to reauthorize the U.S. global HIV/AIDS plan, CQ Politics reports. Under the compromise bill, $50 billion would be allocated for the President's Emergency Plan for AIDS Relief over the next five years -- an increase from the $30 billion the President had previously called for. The new draft, like an earlier version, would remove a controversial provision that requires one-third of HIV prevention funding be spent on abstinence-only education, according to CQ Politics.

Although the compromise measure moves away from the explicit abstinence-only earmark, it calls for "balanced funding" for prevention programs in target countries, including all elements of the ABC approach to HIV prevention -- which stands for abstinence, be faithful and use condoms.

According to CQ Politics, the compromise draft bill also would retain the so-called "anti-prostitution" pledge that an earlier version of the bill had dropped. The compromise bill also would allow funding for HIV testing and education in family planning clinics, but language was dropped from an earlier draft of the bill that would have authorized the use of PEPFAR funds to support contraceptive activities in the context of HIV/AIDS programming. The move to integrate services between HIV/AIDS services and reproductive health groups on the ground has long been sought by Democrats and their allies in the family planning and public health community (Graham-Silverman, CQ Politics, 2/27).

The House Foreign Affairs Committee is scheduled to consider the compromise bill today (CQ Politics, 2/27).

Comments

The Tuesday meeting was the first time that House Foreign Affairs Committee members and White House officials met to discuss the draft bill. Acting committee Chair Howard Berman (D-Calif.) "appeared ready" to move forward with negotiations, CQ Today reports. "I very much want it to be bipartisan, but I also want the program to be effective," Berman said on Tuesday, adding, "Effectiveness is the key."

Democratic committee spokesperson Lynne Weil said it is "very encouraging that the White House and the minority staff finally came to the table on this bill." Bill O'Keefe, senior director for advocacy at Catholic Relief Services, said, "They're all good people who want desperately to preserve the program, and they don't want to do anything to jeopardize what is possibly the most successful U.S. policy venture in the last eight years."

However, some groups have said that a compromise on the reauthorization bill "would be a disappointment" and that a "harsh debate was inevitable," according to CQ Today. "There's nothing about offering contraception to women that isn't going to be turned into something about abortion," Jodi Jacobson, director of advocacy at the American Jewish World Service, said (Graham-Silverman, CQ Today, 2/26).

NPR's "Morning Edition" on Wednesday reported on the PEPFAR bill (Wilson, "Morning Edition," NPR, 2/27). Audio of the segment is available online.

Congressional Democrats Might Use Budget Reconciliation Process To Pass Medicare Bill

Leaders of the House and Senate Budget committees on Tuesday said that they might use the fiscal year 2009 budget reconciliation process to pass a Medicare bill with a provision to prevent a scheduled 10% reduction in physician reimbursements, CQ Today reports. According to CQ Today, use of the budget reconciliation process, which allows legislation to move through the Senate without the threat of a filibuster, is an "attractive option for Democrats who have watched Senate Republicans halt many of their priorities over the past year."

Senate Budget Committee Chair Kent Conrad (D-N.D.) and House Budget Committee Chair John Spratt (D-S.C.) said that they likely will make a decision about whether to use the budget reconciliation process early in the week of March 3 (Clarke, CQ Today, 2/26). Debate on the budget resolution will begin on the Senate floor during the week of March 10 (Johnson, CongressDaily, 2/26).

Senate Finance Committee Chair Max Baucus (D-Mont.) seeks to delay the scheduled reduction in physician reimbursements for 18 months -- a proposal that would cost between $12 billion and $15 billion over five years -- as part of the Medicare bill (Johnson/Cohn, CongressDaily, 2/26). In December 2007, Congress passed legislation that delayed the reduction, previously scheduled to take effect on Jan. 1, for six months (CQ Today, 2/26). Baucus also seeks to expand low-income subsidies for the prescription drug benefit and rural subsidies as part of the Medicare bill.

According to analysts, the Medicare legislation could cost more than $20 billion over five years. "Offsetting that proposal will require Democrats to trim areas that are unacceptable to Republicans, such as private Medicare Advantage plans," CongressDaily reports. Baucus said that "Medicare Advantage is certainly on the table" as a possible source for offsets, as well as individual health care providers and medical education programs (Johnson/Cohn, CongressDaily, 2/26). Republican Response
Senate Budget Committee ranking member Judd Gregg (R-N.H.) on Tuesday criticized the possible use of the budget reconciliation process to pass a Medicare bill. He said Democrats "learned last year that they can use reconciliation as a protection to expand spending in the federal government. I suspect they are going to do that again." He added, "I don't think there is any question they intend to use Medicare Advantage to continue to fund new initiatives" (Johnson, CongressDaily, 2/26).

Senate Minority Whip Jon Kyl (R-Ariz.) said, "In the past we've always used reconciliation to pull back on mandatory spending, reduce taxes, and it certainly is not designed to enable the Congress to spend more money," adding, "And if that's the way it's used, then I think you'll see Republicans resisting very strongly" (Johnson/Cohn, CongressDaily, 2/26).

Opinion Pieces Address Issues Related To Health Care Reform

Summaries of two recent opinion pieces about issues related to health care reform appear below.

• Joseph Dorsey/Donald Berwick, Boston Globe: "The closest you can come to heresy in today's health care policy debate is to suggest that managed care can help and that capitation is the best way to pay for it," Dorsey, former medical director at Harvard Pilgrim Health Care, and Berwick, president and CEO of the Institute for Healthcare Improvement, write in a Globe opinion piece. According to the authors -- who both practiced medicine within a managed care system under the Harvard Community Health Plan -- managed health care "was a great idea when it first emerged, before the term got hijacked by insurance companies that claimed to manage care but in many cases only managed money." They add that, in managed care, details "matter -- a strong focus on patient satisfaction, compensation and incentives, sound leadership, transparent and sophisticated measurement and information" -- and that, when "done right, managed care works." The authors conclude, "Maybe, properly defined and designed, these may not be dirty words after all" (Dorsey/Berwick, Boston Globe, 2/27).
  
  
• Ruth Marcus, Washington Post: "Away from the distorting glare of the campaign trail," a "remarkable thing is happening in the national health care debate": A group of 12 senators has agreed to "sign on to health care legislation" sponsored by Sens. Ron Wyden (D-Ore.) and Bob Bennett (R-Utah) that is "far more radical than anything the presidential candidates have proposed," Post columnist Marcus writes. According to Marcus, the bill (S 334), called the Healthy Americans Act, "would ... blow up the existing health insurance system." The legislation is "based on the premise ... that covering everyone is required for getting costs under control" and has "something for everyone to dislike," she writes, adding, "No one -- not even Wyden and Bennett -- agrees with every aspect of their proposal" (Marcus, Washington Post, 2/27).

Potential Drug Targets Found In Scripps Study Of Sepsis In Mice

"We have identified a key connection of signaling pathways in the cascade of events leading to sepsis. This defines a crucial point where the immune system spirals out of control to cause severe sepsis and where there is an opportunity for therapeutic intervention," says Scripps Research Professor Wolfram Ruf, who led the research with his postdoctoral fellow Frank Niessen. Their results are published in the February 27 advance, online issue of Nature.

Ruf and his colleagues identified a new cross talk involving the vascular coagulation system and certain cells in the immune system. By disrupting this cross talk, they were able to rescue mice from death due to sepsis. Though there is no guarantee this preclinical success will translate into human therapies, these proof-of-principle experiments may improve the diagnosis of heterogeneous sepsis syndromes and yield potent drugs for treating people who suffer from sepsis.

A Severe, Fast-Moving Disease

Sepsis is a severe, fast-moving, dramatic, and often fatal disease caused by an overwhelming bacterial infection that enters the bloodstream. These invading bacteria produce endotoxins and other toxic chemicals that trigger a widespread inflammatory response of the innate immune system - a response that is necessary, as it turns out, because without the inflammation, the body cannot fight off the bacterial infection.

Unfortunately, this inflammation can also spiral out of control leading to septic shock. During sepsis, the inflammation triggers widespread coagulation in the bloodstream. This coagulation can block blood vessels in vital organs, starving the organs of oxygen and damaging them. The organs can be further damaged when the blood starts to flow again because the lining of the blood vessels remain leaky due to inflammatory cytokines and damage by intravascular coagulation. This leads to edema, the buildup of liquid in tissues and allows immune cells to exit the bloodstream and enter the tissue. Inside the tissues, the immune cells can cause severe damage and organ failure. Frequently, the vital function of kidneys and lungs are affected.

Sepsis syndrome can be either fulminant or protracted when patients are not able to cope with and to recover from severe infections. Overall, the prognosis for sepsis is dire. It is one of the leading causes of death for both infants and adults in the United States, and, according to the Centers for Disease Control and Prevention (CDC), it accounted for more than 33,000 deaths in 2004 alone - the last year for which complete statistics are available.

Numerous therapeutic approaches to treating sepsis have been tried through the years. For many years, the only option was to administer powerful, broad-spectrum antibiotics to control the bacterial infection. By the time these were administered, however, it was often too late. The antibiotics did not affect the existing bacterial toxins in the bloodstream, and they could not counter what appeared to be a self perpetuating inflammatory response that results from these toxins. Therapeutic approaches that attempt to reduce inflammation have proven to make people worse off than they were without treatment because those therapies compromise the immune response, unshackling the bacteria in the process.

Another possible approach to intervention involves exploiting the connection between coagulation and immunity, and anticoagulants have proven to be an effective treatment in severe sepsis. In recent years, the U.S. Food and Drug Administration (FDA) approved a recombinant form of activated protein C (Xigris) for treating sepsis, which is believed to work, in part, by controlling coagulation. However, other anticoagulants have failed in clinical trials and recent experiments in mice indicate that Xigris protects the vascular endothelium directly through cell signaling, rather than regulating coagulation.

A New View of Sepsis

The coagulation cascade is a tightly controlled mechanism designed primarily to prevent blood loss due to injury, but is also aberrantly activated in diseases like Ebola and sepsis. Though the link between coagulation and inflammation is one that scientists have known about for years, the exact molecules that connect coagulation to the inflammatory response in sepsis have remained a mystery. Ruf and his colleagues, wanting to understand the process, turned to knockout mice missing signaling receptors for coagulation enzymes, called the protease activated receptors (PARs).

Specifically, they found that mice lacking PAR1, also known as the thrombin receptor, were less likely to die from sepsis. Surprisingly, PAR1-deficient animals initially became very sick when exposed to endotoxin, but recovered more quickly from systemic inflammation and thereby escaped the deadly complication of sepsis syndrome. It turned out that normal mice could also be rescued from death when they received pharmacological drugs that block the PAR1 receptor or very high doses of coagulation inhibitors. This therapeutic intervention was successful, even when inflammation had already peaked. These experiments provided the first clue to indicate that it is the cell signaling component of the coagulation cascade that triggers severe systemic inflammatory response syndromes.

It was originally believed that coagulation in the blood stream damages endothelial cells that line the vasculature. This damage, in turn, helps activate platelets and leucocytes to cause thrombosis and organ damage. Ruf and his colleagues discovered that - unexpectedly - coagulation activates the immune system directly to promote sepsis syndrome. In particular, the dendritic cells of the mouse's immune system play an important role and these cells are perturbed in the lymphatic system, rather than in the blood stream.

Typically dendritic cells produce potent pro-inflammatory cytokines in the lymph nodes during immune reactions. When the dendritic cells sense the increased coagulation in sepsis, they migrate faster through the lymphatic system and as a result do not stay put in the lymph nodes. This causes a release of inflammatory cytokines and chemical signals directly into the lymph. Lymphatic fluid is constantly recycled into the blood stream through the thoracic duct. This major lymph vessel connects to the blood stream immediately before blood enters the lungs. In sepsis, inflammatory mediators in the lymph fluid are thereby directly delivered to one of the most vital organs in the body.

In further research of this novel sepsis mechanism, Ruf and his colleagues uncovered downstream components of the PAR1 signaling pathway. Making use of chemical probes provided by the Scripps Molecular Screening Center, they identified that protease signaling on the dendritic cells induces the production of sphingosine 1 phosphate (S1P), a bioactive lipid that activates another G protein-couples receptor, the S1P receptor 3 (S1P3). In mice that lacked this receptor, they showed that dendritic cells are also responsible for triggering disseminated intravascular coagulation in sepsis. Through the connection between S1P3 and PAR1, dendritic cells are caught in an amplification circuit whereby they activate coagulation, and are in turn excited by one of the enzymes in the coagulation cascade to produce severe systemic inflammation.

Ruf and his colleagues showed that interrupting the S1P3 and PAR1 communication not only prevents the spread of inflammation though the body, but confines the inflammatory reaction to a desired location: the lymph node where the immune system fights microorganisms. This research provides a new view of sepsis and identifies potential targets that might restore a beneficial inflammatory response while blocking the deadly consequences of sepsis. The researchers are now evaluating which targets would be most amenable to clinical development and are testing the broader relevance of this pathway for other infectious diseases.

In addition to Ruf and Niessen, the article, "Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation," was authored by Florence Schaffner, Christian Furlan-Freguia, Rafal Pawlinski, Gourab Bhattacharjee, Jerold Chun, and Hugh Rosen at The Scripps Research Institute and Claudia K. Derian and Patricia Andrade-Gordon at Johnson & Johnson PRD. It appears in the February 27, 2007 issue of the journal Nature.

Support for this work was provided by grants from the National Institutes of Health and from the Deutsche Forschungsgemeinschaft.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus in 2009.

Medicaid Changes; Should Be Suspended Until Change In Administration, Senate Budget Chair Says

Changes in Medicaid rules proposed last week by the federal Centers for Medicare and Medicaid Services should be suspended until the next presidential administration, Senate Budget Committee Chair Kent Conrad (D-N.D.) said Tuesday, CongressDaily reports. Conrad said that a moratorium on four Medicaid regulations could be extended into the next Congress for $1 billion. He added that a longer suspension of the rule changes would be difficult to enact because it would cost $15 billion (Johnson, CongressDaily, 2/27).

The new rules would reduce federal payments for public hospitals, teaching hospitals and services for the disabled, among others. The rule changes would allow states to offer alternative benefit packages called "benchmark" plans, which would provide Medicaid beneficiaries with health coverage that has the same value as plans offered to other individuals in the same state. The proposed rule changes also would allow states to revise existing premium and cost-sharing plans to make them more similar to those allowed under SCHIP.

According to CMS, the rule changes are in line with the Bush administration's "goals of aligning Medicaid more closely with private market insurance and giving states more control over their Medicaid benefits packages." State governors and congressional Democrats have criticized the proposed changes, claiming they would shift billions of dollars in costs to the states, which could lead to cutbacks in services (Daily Women's Health Policy Report, 2/25).

On Tuesday, five governors testified before the House Energy and Commerce Health Subcommittee against the proposed rule changes. Mississippi Gov. Haley Barbour (R) said that he appreciates the Bush administration's moratorium on some Medicaid rules, adding, "It would suit us if you would do that for some of the (other) rules." Georgia Gov. Sonny Purdue (R), Massachusetts Gov. Deval Patrick (D), Ohio Gov. Ted Strickland (D) and Washington state Gov. Christine Gregoire (D) also testified at the hearing (CongressDaily, 2/27).

CMS' proposed changes, which would implement provisions of a 2006 budget reconciliation bill (PL 109-171) and a 2006 package to extend tax provisions (PL 109-432), have a 30-day public comment period (Daily Women's Health Policy Report, 2/25).

Senate Approves Legislation That Would Reauthorize, Overhaul Indian Health Care Improvement Act

The Senate on Tuesday voted 83-10 to approve the Indian Health Care Improvement Act reauthorization bill (S 1200), CQ Today reports (Armstrong, CQ Today, 2/26). The bill would authorize $35 billion over the next decade for the Indian Health Service to expand health coverage and services for about 1.8 million American Indians and Alaska Natives (Holland, Seattle Post-Intelligencer, 2/26).

The bill would:

• Increase the number of American Indians in health care professions;
  
  
• Increase funding for cancer and diabetes screenings, mental health and prevention programs;
  
  
• Prompt construction and modernization of health clinics on reservations; and
  
  
• Expand tribal access to Medicare and Medicaid (Jalonick, AP/Denver Post, 2/26).
  

Joe Garcia, president of the National Congress of American Indians, said, "It's about time, and I applaud the Senate for this historic vote," adding, "Federal prisoners continue to receive better health care than native people, and this is a major step in reversing that alarming statistic" (Casteel, The Oklahoman, 2/27).

The Senate on Tuesday also voted 56-38 to approve an amendment by Sen. Gordon Smith (R-Ore.) that would create a pool of money for health facility construction to be distributed among all tribes, rather than targeting specific tribes. According to Smith, some tribes have never received funding to build health care facilities.

House companion legislation remains in committee, but Rep. Frank Pallone (D-N.J.) said he likely would not make major changes to the Senate measure (CQ Today, 2/26). Pallone said he expects the bill "will move fairly quickly" through the House (Seattle Post-Intelligencer, 2/26).

San Francisco Chronicle Opinion Pieces Discuss Issues Related To Medicare

The San Francisco Chronicle on Wednesday published two opinion pieces that discuss issues related to Medicare. Summaries appear below.

• Spyros Andreopoulos: The Medicare prescription drug benefit "has fulfilled its goal of providing drug coverage to Medicare beneficiaries" but "has failed to protect low-income Americans from high out-of-pockets costs for their medications," Andreopoulos, director emeritus of the Office of Communication and Public Affairs at Stanford University Medical Center, writes in a Chronicle opinion piece. In addition, he writes, "program costs that critics had feared would exceed government projections by as much as $750 billion by the end of the decade have materialized sooner than expected." According to Andreopoulos, the "soaring" costs of the program could "harm Medicare's core mission and the elderly." He writes, "Because a tax increase is out of the question, one obvious solution is to amend" the 2003 Medicare law and "limit the drug benefit." Andreopoulos concludes, "Limiting an entitlement may prove politically impossible, but it would be better to admit that the new law was a mistake and fix it than to cut benefits piecemeal," a move that would "leave the program's future and its recipients in perpetual limbo" (Andreopoulos, San Francisco Chronicle, 2/27).
  
  
• Donna Arduin: "Clearly, the Medicare recovery audit program is working," but a bill supported by the "hospital lobby" would suspend the expansion of the program to protect those who "have built their business models around their annual Medicare windfall," Arduin, president of Arduin, Laffer & Moore: Econometrics, writes in a Chronicle opinion piece. She adds, "Medicare ... drowns in waste and abuse," and, although audits recovered more than $350 million in overpayments in three states in 2007, some lawmakers support the legislation, which would "throw a life preserver to the health care organizations that improperly bill the program for billions of dollars each year." According to Arduin, the bill would suspend the nationwide expansion of the pilot program scheduled for next month until a "laundry list of 'concerns' and 'issues' can be evaluated in depth," although "virtually every concern raised by hospitals has already been addressed by Medicare." The "government calls recovery audits a credible deterrent to improper billing," she writes, adding, "It's no wonder that hospitals and other health care providers ... want the program stopped." Arduin concludes, "Recovery auditing is the life preserver that Medicare needs now" (Arduin, San Francisco Chronicle, 2/27).

Magic' Johnson Calls For More HIV Testing Among Blacks, End To Stigma

As part of his "I Stand With Magic" campaign, former National Basketball Association player Earvin "Magic" Johnson on Tuesday encouraged a crowd of about 300 at the Miami-based Greater Bethel AME Church to be tested for HIV, the Miami Herald reports.

The "I Stand With Magic" campaign, a partnership between the Magic Johnson Foundation and Abbott Laboratories, aims to reduce the number of new HIV cases among blacks by half. Johnson also visited Miami Jackson High School.

Two mobile HIV testing centers were set up outside the church event.

Johnson called on attendees to help eliminate HIV stigma, saying, "We need to urge people to get tested." He added, "We have a major problem, a crisis in our community and only we can take care of it. Blacks and browns, we need to come together."

Florence Greer, a minority AIDS coordinator with the Florida Department of Health, said, "Particularly in the African-American community, we're stressing testing. If you look at four people who are HIV positive, only three people know."

Blacks represent about 20% of the Miami-Dade County population, but 58% of AIDS cases and 46% of HIV cases reported in 2007, according to data from the county Health Department (Lebovich, Miami Herald, 2/27).

Drug Resistant TB Rising Globally, WHO Survey

A new survey by the World Health Organization (WHO) has found the highest rates ever recorded for multidrug-resistant tuberculosis (MDR-TB) globally are occurring today. This is the largest survey on drug resistant TB ever to be conducted, the data for which was collected between 2002 and 2006.

The survey, published Monday 26th February and titled Anti-tuberculosis drug resistance in the world, covers 90,000 TB patients in 81 countries and also found that 45 countries have recorded cases of extensively drug-resistant tuberculosis ((XDR-TB). This is the first time the WHO survey has covered this virtually untreatable form of TB, and because many countries are not equipped to diagnose it, the real picture could be worse.

TB is an infectious airborne respiratory disease caused by a bacteria that is spread by the coughing of infected people. Despite the disease being preventable and curable, 8.8 million people caught it and 1.6 million died in 2005.

If detected early and treated completely, a person with TB can quickly become non-infectious and will eventually be completely cured. However, the bacteria has evolved into numerous drug resistant forms, a scenario that presents public health authorities with major challenges in the campaign to eradicate the disease.

Director of the WHO Stop TB Department, Dr Mario Raviglione, said:

"TB drug resistance needs a frontal assault. If countries and the international community fail to address it aggressively now we will lose this battle."

He added that, as well as confronting resistant forms of TB and saving lives:

"Programmes worldwide must immediately improve their performance in diagnosing all TB cases rapidly and treating them until cured, which is the best way to prevent the development of drug resistance."

There are nearly half a million new cases of MDR-TB globally a year, the WHO estimates from the new survey data. This represents about 5 per cent of all new 9 million TB infections.

The highest incidence of MDR-TB was found in Baku, the capital of Azerbaijan, which lies between Eastern Europe and Western Asia. Here the survey found nearly a quarter of new cases of TB were of the multidrug resistant type.

Other Eastern European and Asian countries were next in line: Moldova (19.4 per cent), Donetsk in the Ukraine (16 per cent), Tomsk Oblast in the Russian Federation (15 per cent), and Tashkent in Uzbekistan (14.8 per cent). These rates exceed the highest levels of drug resistant TB published in the 2004 WHO report.

According to the WHO, there are comparable rates of widespread MDR-TB in China.

The new survey also found a significant association between HIV infection and MDR-TB, typified by the situation in Latvia and the Ukraine where MDR-TB is nearly twice as common in patients with HIV as in TB patients without HIV.

However, all is not doom and gloom and the new report also highlights successes. Estonia and Latvia, two Baltic countries that 13 years ago were classed as drug-resistant TB hotspots, are said to be showing signs of stabilizing, with notification of new TB cases falling. This follows a substantial injection of funds to support a campaign against MDR-TB.

The survey included data on drug resistant forms of TB from only six African countries, not enough to reveal the extent of the problem in a part of the world with the highest overall incidence of TB.

According to the WHO, it is virtually impossible to get data on drug resistant TB in Africa because of lack of the right equipment and staff trained to spot the drug resistant forms of the disease.

Principal author of the report, and TB expert with the WHO, Abigail Wright, said:

"Without these data, it is difficult to estimate the true burden and trends of MDR-TB and XDR-TB in the region."

"It is likely there are outbreaks of drug resistance going unnoticed and undetected," she added.

Nearly 5 billion dollars is needed to establish overall control of TB in low and middle income countries in 2008, estimates the WHO. 1 billion of this is needed for MDR-TB and XDR-TB. But all the money is not yet forthcoming: there is a shortfall of 2.5 billion, which includes a half billion gap for MDR-TB and XDR-TB.

Executive Secretary of the Stop TB Partnership, Dr Marcos Espinal pointed to the seriousness of this shortfall:

"The threat created by TB drug resistance demands that we fill these gaps, as laid out in the Global Plan to Stop TB, a roadmap for halving TB prevalence and deaths compared with 1990 levels by 2015."

America Will Be Spending One Fifth Of GDP On Healthcare By 2017

A new US government analysis estimates that the country's spending on national health will continue to grow steadily and reach nearly 20 per cent of gross domestic product (GDP) by 2017, outpacing economic growth and inflation. GDP is the total value of all goods and services a country produces.

The new analysis was prepared by the Office of the Actuary in the Centers for Medicare and Medicaid Services (CMS) and is published online in the journal Health Affairs. It is also available on the CMS website.

CMS Acting Administrator Kerry Weems, said:

"The cost of health care continues to be a real and pressing concern."

It's not just about the quantity, but the quality as well, said Kerry:

"Making sure we are paying for high quality health care services, not just the number of services provided, is just one of the most critical issues facing the American public and the federal government now and in the future."

The report estimates that growth in US health care spending was 6.7 per cent in 2007 and will remain steady at that rate for the next decade. At this rate, it will grow more rapidly than estimated growth in the general economy (4.9 per cent) and general inflation (2.4 per cent) over the same period.

In 2006, the last year for which full actual figures were included in the analysis, US spending on healthcare was 16.0 per cent of GDP. The CMS estimates this to be 16.3 per cent for 2007 and will grow over the next 10 years to reach a total of over 4.3 trillion dollars, or 19.5 per cent of GDP in 2017.

This overall figure breaks down into many areas of detail, each moving at a different rate. For example:

• Growth in public health spending, due to the implementation of Medicare Part D, is expected to slow down from 8.2 per cent a year in 2006 to 6.8 per cent in 2008.


• Public health spending growth is then expected to rise again, gradually, toward 2017 as the baby boom generation starts to claim Medicare.


• Between now and 2017, growth in health spending is estimated to outpace GDP growth by an average of 1.9 per cent a year.


• This is smaller than the average 2.7 per cent difference over the last 30 years.


• Growth in private health spending, including out of pocket and private insurance, is expected to climb back up to 6.3 per cent a year in 2007, following a dip to 5.4 per cent in 2006, also thought to be due to Medicare Part D.


• This is then expected to peak at 6.6 per cent in 2009, then decelerate to 2017, as the economy slows down in the latter part of the projection period.


• Spending on prescription drugs is expected to slow down from 8.5 per cent in 2006 to 6.7 per cent a year in 2007, mostly reflecting the slower growth in drug prices.


• After that, to 2017, it is expected to accelerate, partly because the growth in dispensing rate for generics will level off, and treatments will increasingly call for earlier drug interventions.


• Medicare Part D is unlikely to affect total national health expenditure growth over the period to 2017 since the per head figure for those on Medicare will be the same as that of those who are not on the program.

Medicare Part D, a program to subsidize prescription drugs for people on the US government's Medicare insurance program for the over 65s and others, came into effect in January 2006.

Kerry urged:

"This projection of health care spending reminds us that we need to accelerate our efforts to improve our health care delivery system to make sure that Medicare and Medicaid are sustainable for future generations of beneficiaries and taxpayers."

The full report tracks health spending by source of funds, including private and public (Medicare, Medicaid), and type of service (hospital, doctors, prescriptions, and so on). The latest estimates start after 2006 and project through to 2017.

Pre-Eclampsia Risk To Mothers And Babies Is Greater For Smokers

The results of a new study published in the journal Hypertension reveal that if women give up smoking before or during pregnancy, they can reduce their risk of pre-eclampsia.

Pre-eclampsia is a high-risk medical condition when hypertension (high blood pressure) arises in pregnancy along with increased protein in urine; it leads to hundreds of baby deaths every year. Women who continue to smoke during pregnancy and who suffer from pre-eclampsia are risking the lives of their unborn children.

It is known that a major public health problem centers on women who smoke while pregnant. Researchers have found that about 30% of pregnant women smoke, resulting in significant health problems to the unborn child. An estimated 4000 fetal deaths (including miscarriages) every year are due to smoking while pregnant, and it can lead to premature births, low birth weight, cot death, and asthma as well as attention deficit and learning problems in childhood.

The study linking smoking and pre-eclampsia was carried out by researcher Fiona Broughton Pipkin of the University of Nottingham and colleagues from the Genetics of Pre-Eclampsia Consortium (GOPEC). Funding was provided by the British Heart Foundation.

"Pre-eclampsia and eclampsia are the second most frequent cause of death in pregnancy in this country and cause an estimated 70,000 deaths worldwide among pregnant women each year. In 2005, 742 babies died as a direct result of pregnancy hypertension in England and Wales. Ten times this number are delivered prematurely for the same reason. They risk short-term breathing problems, potential brain damage and long-term cardiovascular disease. The deaths are the tip of an iceberg for hospital admissions and worry for mothers, babies and families," explains Pipkin.

The multi-center cohort study consisted of 1001 white Western European women with moderate to severe pre-eclampsia and their babies. The researchers found that those in the group who were smokers were more likely to have premature deliveries (before 34 weeks), babies with lower birth weights, or babies with other adverse outcomes. In addition, smokers were five times more likely to develop eclampsia, characterized by convulsions or seizures.

Summarizing the study results, of the 1001 women with pre-eclampsia:

• 34.8% of smokers delivered before 34 weeks (26.8% of former smokers and 21.3% of non-smokers did).
• 46.1% of smokers had underweight babies (37.5% of former smokers and 27.9% of non-smokers did).
• 65.6% had babies with adverse outcomes (60% of former smokers and 50.4% of non-smokers did).

"Research like this study from The University of Nottingham is vital to help us understand the full effects of lifestyle choices on our heart and circulatory health and that of our children. Smoking is clearly potentially very harmful to mother and baby, and we need to support women in quitting at every stage of pregnancy," reports Ellen Mason, a cardiac nurse at the British Heart Foundation (BHF).

Professor Pipkin adds: "Although a recent article suggested that smoking in pregnancy is less damaging to the unborn baby than commonly supposed, GOPEC argues that smoking CAN make a bad situation worse for both mother and baby in pre-eclampsia."

They find that stopping smoking limits the damage.

"I feel very strongly that pregnant women should be encouraged as actively as possible to stop smoking, and this paper provides yet more reasons why," concludes Pipkin.

Researchers from the University of Nottingham, in a separate study, will analyze 1050 pregnant women to see the effects of using nicotine patches during pregnancy. The Smoking, Nicotine and Pregnancy (SNAP) trial (a £1.3m clinical trial) will study the safety and effectiveness of nicotine replacement therapy (NRT) for expectant mothers who wish to give up smoking, as well as effects on the child's behavior and development.

What Women Think During Their First Pregnancy

Pregnant women who perceive having a well-balanced relationship with their parents during their childhood will experience fewer difficulties in the transition to motherhood, as opposed to women whose relationship with their parents was characterized by unresolved anger or rejection reveals a new study conducted at the University of Haifa. The study also found that women who tend to deny negative experiences in early childhood relationships expected to experience a relationship with their future children characterized by less warmth compared to other women who participated in the study.

The research, which was conducted by Ora Gazit under the direction of Dr. Miri Scharf, examined 160 Jewish women in the last trimester of their first pregnancy who live with their husband or partner. The researchers examined the expectations, thoughts and emotions of the pregnant women regarding themselves as future mothers and their future relationships with their babies based on two approaches related to identity building. The first focuses on the way people perceive their early childhood relationship with their parents and how this is reflected in their thoughts, perceptions and behavior during their lives. The second focuses on existing differences between people whose motivation is derived from an aspiration for success and those who are motivated by an aspiration to avoid failure.

The results of the study revealed that women whose early childhood relationships with their parents were characterized by rejection and unresolved conflicts, expected to experience a high measure of separation anxiety, thought their child would be more demanding of them and thought they would set a lot boundaries, compared to other women in the study.

Among women who described their early childhood relationships with their parents as being characterized by rejection but who had difficulty recalling many of the events representative of this relationship, the study found a majority had positive thoughts about their impending motherhood and towards their unborn child. However, in comparison to the remainder of the women in the study, they expected to develop a less warm and close relationship with their baby. The women who had a balanced view of their early relationship with their parents had the most optimal expectations towards their impending motherhood. They expected to feel a low level of separation anxiety from their child, thought childrearing would be easy and that their relationship would be characterized by warmth.

In addition, the study found that women who were characterized by wanting to advance and reach set goals were positive and more optimistic, in comparison to women who were characterized by abstention and concern with self-defense, security and responsibility. According to the researchers, women in the first group thought they would be more fulfilled in parenthood, saw themselves and their child in a more positive light, thought they would be more productive and warm as mothers and expected to have good communication with their child. "The results of the research show that there is great importance in evaluating thoughts, perceptions and feelings about parental identity during pregnancy. Such an evaluation will enable early identification of women who are concerned they will have difficulty contending with parental roles and offer them tools that will help them adapt better to the transition to motherhood," summarized the researchers.

Anorexics Who Commit Suicide Use Extreme Methods, Leaving Little Doubt Of Intent

A disturbing new study, notable during this Eating Disorder Awareness Week, challenges assumptions that the high suicide rate among anorexics can be explained by compromised physical health that leads to death from the slightest attempt. Research to be published in the Journal of Affective Disorders shows that anorexics who are suicidal use highly lethal methods suggesting an overwhelming wish to die.

According to lead author, University of Vermont assistant professor of psychology Jill Holm-Denoma, while psychiatrists and other doctors have long observed that people with anorexia nervosa die by suicide at surprisingly high rates, there had been no data about what methods they were using to kill themselves. The assumption was often that these are people on the verge of death anyway; they are so malnourished and underweight that the smallest suicide attempt could easily lead to death.

Holm-Denoma's research, however, suggests a different explanation. Among anorexics who commit suicide, the methods used tend to be overwhelmingly lethal in conjunction with a low potential for being rescued, means that would be likely to kill anyone. She found that women (the vast majority of people who suffer from anorexia) were burning themselves, jumping in front of trains and hanging themselves, among other extreme acts.

"I wouldn't say that a defining feature of anorexia is a wish to die," says Holm-Denoma, "but among the subgroup of people with anorexia who attempt suicide, they have a strong wish to die and they engage in an act of self injury that has a very high likelihood of killing them right away."

Holm-Denoma, an expert on treating eating disorders, is available to discuss this research as well as other aspects of eating disorders. Approximately one percent of adolescent and young adult females suffer from anorexia and about twice as many have bulimia. And the population of people with eating disorders is growing outside of the traditional group, notably young, white, middle- to- upper- middle-class women. According to Holm-Denoma, as racial and ethnic minorities, as well as older women, are increasingly becoming media targets for the thin ideal, clinicians are seeing a rise in eating disorders from groups once thought to be protected.

Both anorexia and bulimia are also associated with high rates of mood, anxiety, substance use and personality disorders. A third category of eating disorder, binge eating, afflicts up to four percent of the population, and affects men and women equally. The combined effects take a huge toll. Anorexia, in fact, has the highest mortality rate of any psychiatric disorder.

Mounting Evidence Of Increased Mortality From Drug Used By Anemic Cancer Patients

Millions of cancer patients take drugs to boost their red blood cells and health when they become anemic after chemotherapy. But a new study by Northwestern University's Feinberg School of Medicine shows these drugs, called erythropoiesis-stimulating agents (ESAs), actually raise patients' risk of death, possibly by stimulating the growth of cancer cells.

A meta-analysis of 51 trials with 13,613 patients revealed a 10 percent increased risk of death among cancer patients taking ESAs compared to patients who did not take them. The study, lead by Charles Bennett, M.D., the A.C. Buehler Professor in Economics and Aging at the Feinberg School, will be published in the Journal of the American Medical Association today, February 27.

The Northwestern study is the first to demonstrate a quantifiable increased risk of death from EPAs and is based on the largest number of trials ever examined for this purpose.

"The FDA says if you use the drug in moderation, it should be safe," Bennett said. "But our findings, in conjunction with basic science studies, raise the concern that the drug may be stimulating cancer and shortening cancer patients' survival."

"It's troubling that 15 years after the drug came out, we finally came to this realization," said Bennett, who also is a hematologist and oncologist at Northwestern Memorial Hospital and the Jesse Brown VA Medical Center.

The JAMA paper is an update of a poster presentation Bennett made to the American Society of Clinical Oncology in June 2007.

One of the study's co-authors, Stephen Lai, M.D., assistant professor at the University of Pittsburgh Medical Center, tested the response of cancer cells to an ESA in the laboratory. Lai, a head and neck surgeon, saw a significant effect when he added an ESA called erythropoietin to head and neck cancer cells in tissue culture.

"We saw a dramatic change," Lai said. "Adding 'epo' (erythropoietin) to the cells increased their ability to migrate or invade. Our basic science findings and the clinical trial results suggest that giving cancer patients 'epo' for their anemia may actually cause their tumors to progress."

Lai's basic science study is part of a growing body of studies that demonstrate erythropoietin expression and function in a variety of human cancers as presented at a National Cancer Institute workshop on erythropoietin and tumor progression December 2007 in Bethesda, Md.

The FDA approved the ESAs erythropoietin and darbepoetin in 2003 as a treatment for anemic cancer patients to avoid blood transfusions. However, evidence linking these drugs to a higher risk of death has been mounting. In March 2007, the FDA issued a public health advisory on EPAs, warning of an increased risk of serious and life-threatening side effects.

Ironically, Bennett noted, "The later clinical trials were conducted to see if these drugs help people live longer. But, it turns out, this is not the case."

ESAs produced up to $6 billion in cancer-anemia related sales last year for pharmaceutical firms, Bennett said, and represented Medicare's largest pharmaceutical expenditure.

Bennett began investigating these drugs when the study's senior author, Michael Henke, M.D., professor of medicine in radiation oncology at the University of Freiburg in Germany, first raised an alarm in 2003. For the new study, Bennett and his co-authors updated a 2006 analysis by the Cochrane Collaboration with more recent statistics from 13 additional Phase III trials. The 2006 Cochrane study did not show an increased risk of death, Bennett said.

"This is why it's important to continuously look at the data," Bennett said. "You can't let it fall by the wayside. Just a year out of date is not acceptable. Importantly, the more recent clinical studies were larger and addressed the issue of survival."

The Northwestern study also confirmed a previously known 57 percent increased risk of blood clots in the legs or lungs for cancer patients receiving ESAs. But the higher blood clot risk did not explain the 10 percent increased risk of death shown in his study, Bennett said.

"We know that ESA's may prevent a blood transfusion, but if I had cancer and I needed a blood transfusion, I would be much more conservative about taking ESAs," Bennett said. "The current FDA recommendation is these drugs are safe for cancer patients as long their hemoglobin levels aren't raised too high. Our data do not support that."

Lai cautioned that various solid tumors such as breast cancer, colon cancer and melanoma may react differently to ESAs. "The exact effect and size of that effect may be different depending upon the type of tumor. Additional research is clearly necessary, and we have to be careful about generalizing these results before further research is conducted," he said.

On March 13, the FDA's Oncologic Drugs Advisory Committee will meet in Gaithersburg, Md. to discuss the cumulative data, including the recent study results, regarding the use of ESAs for cancer patients, Bennett said.