New Guidelines Reveal The Complexity Of Food Allergy Management

Allergists representing three organizations developed evidence-based guidelines for food allergy diagnosis and management, which has become more sophisticated and challenging in recent years due to the increase in prevalence of certain food allergies and important scientific developments.

The Joint Task Force guidelines, “Food Allergy: A Practice Parameter,” are published this month in Annals of Allergy, Asthma & Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology (ACAAI). The Joint Task Force on Practice Parameters, representing the ACAAI, the American Academy of Allergy, Asthma and Immunology (AAAAI) and the Joint Council of Allergy, Asthma and Immunology (JCAAI), has published 20 practice parameters for the field of allergy-immunology.

“The practice parameter on food allergy represents more than 10 years of research and investigation of literature by members of the Joint Task Force,” said Jean A. Chapman, M.D., Cape Girardeau, Mo., a chief editor. “Designed to improve patient care, the guidelines provide practicing physicians with an evidence-based, broadly accepted approach to the diagnostic evaluation and management of IgE-mediated (allergic) food reactions.”

Although adverse food reactions have been reported in up to 25 percent of the U.S. population at some point in their lives, the prevalence of food allergy, an IgE-mediated response to a food, is much lower than the number of suspected food allergies. It varies between 2 percent (adults) and 5 percent (children) in most studies, and is higher in individuals with atopic dermatitis, certain pollen sensitivities or latex sensitivities.

“The guidelines reinforce the need for physicians to think about food allergy as the potential cause of a patient’s symptoms, whether it be GI complaints or skin problems,” said John Oppenheimer, M.D., UMDNJ-New Jersey Medical School, New Brunswick, N.J., a chief editor of the practice parameter.

“Likewise, if a patient has a list of foods they think they are allergic to, it’s important to differentiate what’s truly an allergy and what isn’t. If a patient is trying to avoid 10 or 15 foods, it becomes really cumbersome, and if someone does have an allergy on that list, it is much more difficult to avoid the important allergen,” Dr. Oppenheimer said.

Food allergies are more common in children than in adults. According to the authors, the most common food allergens in infants and young children are cow’s milk, hen’s egg, peanut (a legume), tree nuts, soybeans and wheat. Although sensitivity to most allergens is lost in late childhood, allergy to peanut, tree nut and seafood is likely to continue throughout the patient’s life. Only approximately 20 percent of children with peanut allergy lose their sensitivity. The most common foods causing allergy in adults are peanuts, tree nuts (walnut, hazelnut, Brazil nut, and pecan), fish, crustaceans, mollusks, fruits and vegetables.

“The most important diagnostic tool is the patient’s history. Is there an association between eating the food and having symptoms?” said Jay M. Portnoy, M.D., Section of Allergy, Asthma & Immunology, The Children’s Mercy Hospital; professor of pediatrics, University of Missouri-Kansas City, School of Medicine, Kansas City, Mo.; and associate editor of the practice parameter. “Hidden food allergy is uncommon. Most food allergies occur with a direct relationship – you eat the food, then you have a reaction. It is usually a pretty obvious reaction.”

Due to recent developments in laboratory technology, Dr. Oppenheimer said it has become common practice for physicians to order blood tests for 20 or 30 foods when testing for other allergies, even when there is no history of allergic food reactions. “Being a good historian and culling down what foods you think are important should determine what types of tests are done,” he said.

A detailed discussion of skin prick or puncture tests, serologic tests for specific IgE and oral food challenges is provided in the practice parameter.

“Just because you have a positive test to a food doesn’t mean you are allergic to the food,” Dr. Portnoy said. “It is really important that the symptoms correspond to the test. Personally, I’m still seeing a lot of patients who have been told by a physician not to eat foods because of positive test results, when in fact they have never had a problem with the food. You don’t want to avoid food that you are not allergic to, but you do want to avoid foods that you are allergic to. Allergists can be helpful in determining this because they have special training and experience in interpreting the test results.”

The guidelines recommend carrying more than one epinephrine auto-injector because anaphylactic reactions may be prolonged; to seek immediate medical care after a reaction; and to be monitored for an appropriate period. Most fatal and near-fatal food allergic reactions in the United States are caused by peanut and tree nuts, often with delayed administration of injectable epinephrine.

“The treatment for food allergy is to avoid the food. Inevitably, you’re going to have accidental exposure. It just happens, even to the most careful person. If you’ve got a true, IgE food allergy, you should carry self-injectable epinephrine, even if you’ve only had hives before. The next time if you get a higher exposure, you may have a life-threatening reaction. You should also wear a medical alert bracelet,” Dr. Portnoy said.

The guidelines include recommendations for food allergy management in special settings and circumstances, where patients have an increased risk for unintentional food allergy exposure.

“From the perspective of schools and child care, parents should partner with the administrative staff and teachers or child care workers to determine what avoidance maneuvers may be lacking. It’s important they understand when acute care is needed, how to respond and when it’s appropriate to administer epinephrine,” Dr. Oppenheimer said.

Sections of the practice parameter discuss successful avoidance, risk factors and prevention of food allergy. Cross-reactivity of food allergy, adverse reactions to food additives, genetically modified foods, and future directions also are discussed.

The guidelines list the Food Allergy and Anaphylaxis Network (FAAN) as a resource for patient information on food avoidance. Anne Munoz-Furlong, founder and CEO of FAAN, said the new food allergy guidelines will impact patients in a number of ways.

“First of all, it’s going to give them better and quicker diagnosis of food allergy and that’s going to be a key factor in improving the patient’s and the family’s quality of life,” said Ms. Munoz-Furlong. “I think that while some clinicians are very familiar with food allergy, others rarely see patients with this allergic disorder. The guidelines provide a comprehensive summary and will serve as a good reference tool for both groups of clinicians.

“Additionally, it will improve patient care. Our most common questions from patients are about interpretation of diagnostic tests and whether they should avoid the 30 or so foods their doctor told them to avoid. The information to the clinicians about being careful about diagnostic tests, how to interpret those tests, and being aware of the implications of an over-restrictive diet is going to be an improvement for patients,” she said.

Patient information on food allergies and other allergic diseases is available by calling the ACAAI toll free number at (800) 842-7777 or visiting its Web site at http://www.acaai.org. For food allergy patient information or support, call FAAN at 800-929-4040 or visit online at http://www.foodallergy.org.

The ACAAI is a professional medical organization comprising more than 5,000 qualified allergists-immunologists and related health care professionals. The College is dedicated to the clinical practice of allergy, asthma and immunology through education and research to promote the highest quality of patient care.

Citation: Chapman JA, Bernstein IL, Lee RE, Oppenheimer J, et al. Food Allergy: A Practice Parameter. Ann Allergy Asthma Immunol 2006;96, Number 3, Supplement 2.

http://www.acaai.org

FDA Updates Its Nationwide Alert On Counterfeit One Touch Blood Glucose Test Strips – Actions Constitute A Class I Recall

The U.S. Food and Drug Administration (FDA) is providing an update to its notifications on October 13, and October 23, 2006, alerting the public to counterfeit blood glucose test strips being sold in the US for use with various models of LifeScan, Inc., One Touch Brand Blood Glucose Monitors. These test strips are used by people with diabetes to measure their blood glucose. Today’s update includes an additional lot number that is being distributed, along with a description of how to identify the new lot.

FDA has classified the current situation as a Class I recall because some of the counterfeit products have significant deviations in performance. The counterfeit test strips potentially could give incorrect blood glucose values– either too high or too low–which might result in a patient taking either too much or too little insulin and lead to serious injury or death.

The products of concern are counterfeit – they are not marketed or distributed by Lifescan, and Lifescan is not responsible for conducting the recall. Rather, firms that are distributing the counterfeit product are responsible for conducting the recall using corrective actions developed by Lifescan, with input from FDA. FDA continues to work with Lifescan and the distributors to ensure that counterfeit products are removed from the market.

The counterfeit test strips are:

– One Touch® Basic®/Profile® (lot #272894A, 2619932, 2606340, 2615211 (added October 23, 2006) and 227078A (new lot)) test strips, and
– One Touch® Ultra® (lot #2691191 and 2691261 (added October 23, 2006) test strips.

LifeScan, Inc. alerted FDA of the new lot of counterfeit test strips. The FDA continues to investigate the matter, including whether there have been any adverse events associated with this counterfeit product.

Consumers who have the counterfeit test strips should stop using them, replace them immediately and contact their physician. Consumers with questions may contact LifeScan, Inc. at 1-866-621-4855. Consumers who have discarded the outer box or do not know the lot number of their test strips should stop using those test strips and replace them.

The counterfeit test strips were distributed to pharmacies and stores nationwide by various distributors.

How to Identify

For complete information on how to identify the counterfeit test strips, please check LifeScan’s web site.

The following characteristics may help to identify the counterfeit test strips:

Counterfeit One Touch Basic/Profile Test Strips, lot numbers 272894A, 2619932, and 2606340

– Lot Numbers 272894A, 2619932, or 2606340 appears on the outer carton and on the inside container (vial).
– The outer carton is written in Multiple Languages including English, Greek and Portuguese.
– The outer carton is labeled as 50-Count One Touch (Basic/Profile)Test Strip packages
– The bottom of the outer carton does not include an NDC number.

Counterfeit One Touch Basic/Profile Test Strips, lot numbers 2615211 and (227078A (new lot))

– Lot Numbers 2615211 or 227078A appear on the outer carton and on the inside container (vial).
– The outer carton is written in English.
– The outer carton is labeled as 50-Count One Touch (Basic/Profile) Test Strip packages.
– A picture of a hand appears on the test strip displayed on the outer carton.
– The inside container (vial) is labeled as “plasma calibrated”
– The bottom of the outer carton does not include an NDC number.

Counterfeit One Touch Ultra Test Strips, lot numbers 2691191 and 2691261

– The lot numbers 2691191 or 2691261 appears on the outer carton and on the inside container (vial).
– The outer carton and inside container (vial) is written in both English and French.
– The outer carton is labeled as 50-Count One Touch Ultra Test Strip packages.
– The bottom of the outer carton does not include an NDC number.

On October 13, 2006 (later updated October 26, 2006), LifeScan alerted the public via a press release and notified pharmacists, distributors, and wholesalers through a letter. The firm advised customers to contact their original source of supply for restitution. For more information, visit http://www.Lifescan.org.

On October 13, 2006 (later updated October 23, 2006), FDA alerted its Counterfeit Alert Network partners, a coalition of healthcare professional, consumer and trade associations, who have agreed to further disseminate this important information in a timely and effective manner. For more information about this and other counterfeit products, visit http://www.fda.gov/counterfeit.

Any adverse reactions experienced with the use of this product, and/or quality problems should also be reported to the FDA’s MedWatch Program by phone at 1-800-FDA-1088, by Fax at 1-800-FDA-0178, by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at http://www.fda.gov/medwatch.

Hecht Honored With AACR-Cancer Research And Prevention Foundation Award For Ground-breaking Research

Stephen S. Hecht, an internationally recognized expert on cancer-causing agents in tobacco and the pathways by which they cause cancer, has been selected to receive the fifth annual American Association for Cancer Research (AACR)-Cancer Research and Prevention Foundation (CRPF) Award for Excellence in Cancer Prevention Research.

Dr. Hecht, the Wallin Professor of Cancer Prevention and the American Cancer Society Research Professor at The Cancer Center at the University of Minnesota, is being honored for more than three decades of research on tobacco and its link to cancer formation and growth.

Over this span of time, Dr. Hecht has been the most cited author on tobacco carcinogenesis, and is generally recognized as the world’s leader in research on tobacco-specific human carcinogens called nitrosamines, found in cigarette smoke and smokeless tobacco. Other work in his laboratory, showing that exposure to second-hand tobacco smoke resulted in the presence of tobacco-specific carcinogens in nonsmokers    has had a profound impact on clean indoor air laws critical for tobacco control.

“Stephen Hecht’s ground-breaking and detailed research on tobacco-specific nitrosamines has enhanced our understanding of tobacco carcinogenesis,” said Dr. Margaret R. Spitz, chair of the Department of Epidemiology at The University of Texas M. D. Anderson Cancer Center and co-chair of the award selection committee. 

“His research has provided a strong scientific rationale for public policies on smoking restriction.”

Added Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR:  “Dr. Hecht has been, and continues to be, among the most recognized scientists in the world studying the impact of tobacco and tobacco products on lung cancer. His critical work in this field – marked by its thoroughness, breadth and extraordinary high quality — is helping to save countless lives from this devastating disease.”

??It was 1974 when Dr. Hecht, along with Dr. Dietrich Hoffmann, provided the first demonstration of organic carcinogens – nitrosamines — in unburned tobacco. The two scientists identified substantial amounts of a specific nitrosamine called N’-nitrosonornicotine (NNN) in unburned tobacco, suggesting that smokeless tobacco was not a harmless substitute for cigarettes. This work ultimately led to the regulation of smokeless tobacco products.

Dr. Hecht subsequently reported the first synthesis of another nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and he demonstrated its formation from nicotine during the curing process. He further showed that exposure to NNK resulted in lung cancer in laboratory mice and rats, and then characterized how NNK caused lung cancer. In highly detailed studies, Dr. Hecht determined virtually all the known pathways of metabolism of NNK, and later showed the chemical binding of DNA to metabolically activated NNK, NNN and other tobacco-related nitrosamines – steps that are critical to the initiation of cancer.

These studies led to the development of biomarkers – substances that can be measured in blood or urine – to help identify individuals most susceptible to the cancer-causing effects of tobacco products. Such biomarkers also can help determine exposure of non-smokers to second-hand tobacco smoke. Dr. Hecht demonstrated the presence of a metabolite of NNK in the urine of non-smokers exposed to second-hand tobacco smoke in various settings. The metabolite, NNAL, also was discovered in the fetuses and newborns of smoking mothers. Such evidence provided the rationale for tobacco control laws in public places.

Another area of research in the Hecht lab is the identification and development of naturally occurring chemopreventative agents that may help protect smokers from later disease. Current work in this area involves compounds found in cruciferous vegetables, nuts and fruit. Phase II studies to evaluate the efficacy of these agents in smokers and ex-smokers are now being planned.

Other past winners of AACR-CRPF Award for Excellence in Cancer Prevention include Scott M. Lippman, M.D. of The University of Texas M. D. Anderson Cancer Center, in 2005; David S. Alberts, M.D., of the Arizona Cancer Center, in 2004; Waun Ki Hong, M.D., also of the M. D. Anderson Cancer Center, in 2003; and Michael B. Sporn, M.D., of the Dartmouth Medical School, in 2002.

Dr. Hecht graduated from the Duke University, with a degree in chemistry. He was awarded a Ph.D. in organic chemistry from the Massachusetts Institute of Technology, where he also did postdoctoral research in mass spectrometry. Prior to moving to the University of Minnesota in 1996, for 23 years Dr. Hecht conducted research at the American Health Foundation in Valhalla, N.Y., where he was Director of Research from 1987-1996. At the University of Minnesota, he is Head of the Carcinogenesis and Chemoprevention Program at the Cancer Center, Co-director of the Transdisciplinary Tobacco Use Research Center, and a member of the Medicinal Chemistry graduate department.

Dr. Hecht, who has authored or co-authored more than 600 publications, holds a Merit Award and was previously the recipient of an Outstanding Investigator Grant, both from the National Cancer Institute. In 2000, he was named an American Cancer Society Research Professor, one of about 40 in the country. Dr. Hecht has served on several International Agency for Research on Cancer working groups, was a contributor to the 2005 Surgeon General’s Report on Passive Smoking and Health, and is chapter editor for cancer in the upcoming Surgeon General’s Report on How Tobacco Causes Diseases. He also has participated on numerous government and international committees including the National Cancer Institute’s Board of Science Counselors, the National Toxicology Program Board of Scientific Counselors, and the National Center for Toxicological Research Science Advisory Board.

He is active in the AACR, where he has served on program committees for national and special meetings, and on the steering committee of the Chemistry in Cancer Research Working Group.

Dr. Hecht will give an award lecture titled, “A Tobacco-Specific Lung Carcinogen: from Basic Research to Tobacco Control,” on Tuesday, November 14, at the Fifth Annual AACR International Conference on Frontiers in Cancer Prevention Research. This premier meeting on cancer prevention research will be held November 12-15, 2006 at the Hynes Convention Center in Boston, Mass.

The AACR is pleased to co-sponsor this award with the Cancer Research and Prevention Foundation. CRPF is a national, nonprofit health foundation with a single mission: the prevention and early detection of cancer through scientific research and education.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment.  AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

http://www.aacr.org

Poniard Announces Positive Interim Survival Results From Ongoing Phase 2 Trial Of Picoplatin For Small Cell Lung Cancer

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a specialty pharmaceutical company focused on oncology, today announced positive interim median overall survival data from its ongoing Phase 2 clinical trial of picoplatin in patients with small cell lung cancer (SCLC). The trial includes SCLC patients with platinum-refractory disease or platinum-resistant or platinum-sensitive disease who have progressed within six months after receiving first-line therapy. Based on these data, Poniard plans to initiate a pivotal Phase 3 trial of picoplatin in SCLC in the first half of 2007 and file a New Drug Application for this indication in 2009. The Company anticipates that the primary endpoint of the planned Phase 3 trial will be survival and expects to enroll approximately 400 patients in the trial.

Picoplatin is a new generation platinum therapy with an improved safety profile designed to overcome and prevent platinum resistance associated with chemotherapy in solid tumors.

“SCLC presents a critical unmet medical need with inadequate treatment options,” said John R. Eckardt, M.D., a Phase 2 clinical trial investigator and medical oncologist at The Center for Cancer Care and Research in St. Louis. “Platinum-resistant or -refractory SCLC patients often experience rapid disease progression and low overall survival despite treatment with available drugs, which have significant associated toxicities.”

No new drugs have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of platinum-resistant or -refractory SCLC in nearly a decade.

“It appears that in addition to potentially extending survival in these patients, picoplatin may offer better quality of life because of its improved safety profile over current treatment options,” said Jerry McMahon, Ph.D., chairman, president and CEO of Poniard. “We believe that the planned Phase 3 SCLC trial will be an important step forward on the path to market for picoplatin. We also believe our current financial resources will enable us to initiate the Phase 3 study, complete our ongoing Phase 2 trial in SCLC, and initiate and complete patient enrollment in our planned Phase 2 studies in colorectal and prostate cancers next year.”

Summary of Interim Phase 2 Survival Results

Enrollment in the open-label, multi-center Phase 2 trial was completed in August 2006. This ongoing trial is designed to confirm the clinical activity of picoplatin as second-line therapy in patients with platinum-refractory disease or disease that has progressed within six months following first-line treatment with a platinum-based chemotherapy, such as cisplatin or carboplatin.

A recent interim analysis showed a median overall survival of 26.7 weeks in the 72 evaluable patients treated with picoplatin. According to the 2006 National Comprehensive Cancer Network practice guidelines, the median survival for patients who receive second-line chemotherapy is approximately 16 to 20 weeks.

At the time of the interim analysis, there had been 22 deaths from disease progression among the 77 picoplatin-treated patients. There were not sufficient data on the last five patients enrolled in the Phase 2 study to include them in the interim analysis. However, data for all patients will be included in the final analysis.

In addition to overall survival, the Phase 2 trial is evaluating overall response rates, progression-free survival, improvement in disease-related symptoms and disease control. Final results of this trial are expected in mid-2007 and will be submitted for presentation at upcoming scientific conferences.

“The median overall survival observed to date in our Phase 2 trial confirms our previous data and suggests that picoplatin treatment may represent an improvement over best supportive care alone,” said David A. Karlin, M.D., senior vice president of clinical development and regulatory affairs of Poniard. “We have designed our Phase 3 trial with these observations in mind and are regularly communicating and working closely with the FDA in our efforts to bring this drug to market for these severely underserved patients.”

Poniard’s planned international, multi-center, randomized Phase 3 pivotal trial is expected to take about 20 months to complete, with a 2:1 randomization comparing picoplatin plus best supportive care to best supportive care alone. The planned trial would enroll patients who are refractory to, or who have progressed within six months of completing, treatment with first-line platinum chemotherapy (cisplatin or carboplatin). Beyond the primary endpoint of overall survival, the study would also measure overall response rates, progression-free survival and disease control.

About Small Cell Lung Cancer

SCLC is the most aggressive and deadly form of lung cancer and accounts for approximately 20 percent of all lung cancer cases. The current two-year survival rate for patients with extensive SCLC is less than 10 percent with current management options. The estimated incidence of lung cancer in the United States in 2006 is 174,500, according to the National Cancer Institute. The estimated incidence in Europe in 2004 was 383,900, according to the International Agency for Research on Cancer. Poniard received orphan drug designation in November 2005 from the FDA for picoplatin for the treatment of SCLC.

SCLC is currently treated with platinum therapies, but many patients do not respond, and if they do respond, they typically relapse within a short time after treatment. There is currently no FDA-approved therapy and no consistent and effective therapy for SCLC patients who have platinum-resistant or -refractory disease after treatment failure with first-line combination therapy with either cisplatin or carboplatin.

About Poniard Pharmaceuticals

Poniard Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on the discovery, development and commercialization of innovative oncology products to impact the lives of people with cancer. Picoplatin, the Company’s lead product candidate, is a new generation platinum therapy with an improved safety profile. An intravenous chemotherapeutic agent, it is designed to overcome and prevent platinum resistance associated with chemotherapy in solid tumors. Picoplatin is currently being studied in clinical trials for the treatment of small cell lung, colorectal and hormone- refractory prostate cancers. As part of the Company’s strategic goal of building a diverse oncology pipeline, the Company also is collaborating with the Scripps Florida Research Institute on the discovery of novel, small- molecule, multi-targeted protein kinase inhibitors. For additional information please visit http://www.poniard.com.

This release contains forward-looking statements, including statements regarding the Company’s business model, drug development program and clinical trial plans and preliminary results to date. The Company’s actual results may differ materially from those indicated in these forward looking statements based on a number of factors, including anticipated operating losses, uncertainties associated with research, development, clinical trials, the results of later clinical testing and related regulatory approvals, future capital needs and uncertainty of additional financing, competition, uncertainties associated with intellectual property, dependence on third-party manufacturers, suppliers and collaborators, lack of sales and marketing experience, loss of key personnel, uncertainties associated with market acceptance, technology change and government regulation, general market conditions and the other risks and uncertainties described in the Company’s current and periodic reports filed with the Securities and Exchange Commission, including the Company’s Annual Report on Form 10-K for the year ended December 31, 2005, and its Quarterly Report on Form 10-Q for the quarter ended June 30, 2006. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. The Company undertakes no obligation to update any forward-looking statement to reflect new information, events or circumstances after the date of this release or to reflect the occurrence of unanticipated events.

Poniard Pharmaceuticals, Inc.
http://www.poniard.com

UC Davis Study With Mice Links Thimerosal With Immune System Dysfunction

A team of cell biologists, toxicologists and molecular bioscientists at the University of California, Davis, has published a study connecting thimerosal with disruptions in antigen-presenting cells known as dendritic cells obtained from mice. The study provides the first evidence that dendritic cells show unprecedented sensitivity to thimerosal, resulting in fundamental changes in the immune system’s ability to respond to external factors. The study was published online today and will be available in the July print edition of Environmental Health Perspectives, the peer-reviewed scientific publication of the National Institute of Environmental Health Sciences.

“This is the first time that thimerosal has been shown to selectively alter the normal functions of dendritic cells,” said Isaac Pessah, a toxicologist with the UC Davis School of Veterinary Medicine, director of the Children’s Center for Environmental Health and Disease Prevention and senior author of the study. “Dendritic cells play pivotal roles in overcoming viral and bacterial invaders by coordinating the immune system’s overall combat response.” One dendritic cell can activate as many as 300 T-cells–white blood cells that help find and kill external agents that attack the immune system–making them the most effective immune system activators.

The study shows how intricate connections between calcium channels in dendritic cells change when exposed to thimerosal. “The slightest fluctuation in how calcium channels ‘communicate’ can alter the growth, maturation and activation of dendritic cells,” explained Pessah. “Thimerosal dramatically alters how two key calcium channels, code-named RyR1 and IP3R1, found in dendritic cells function as a team by ‘garbling’ the normal signaling system between them.”

When thimerosal at a concentration as low as 20 parts per billion alters the fidelity of normal calcium signals, dendritic cells show abnormal secretion of IL-6 cytokine–a potent chemical signal that initiates inflammatory responses. Higher concentrations–200 parts per billion–causes programmed death of dendritic cells, preventing them from maturing and doing their primary job of activating T-cells. Without proper feedback to guide its response, a normal dendritic cell can quickly become “a rogue, producing misinformation that could activate aberrant and harmful immune responses,” Pessah explained. “Even one rogue dendritic cell can activate many inappropriate immune responses.”

The research team conducted the study on cells cultured from a strain of mouse not particularly susceptible to immune dysregulation. Using fluorescent stains and powerful microscopes to study both immature and mature dendritic cells from bone marrow cultured under normal physiological conditions, the researchers discovered that extremely small levels of thimerosal interfere significantly with calcium channel function after just a few minutes of exposure. They also observed that immature dendritic cells are particularly sensitive to thimerosal.

Thimerosal is a cheap and effective mercury-based preservative. Its potential effects on embryonic neuron development led to its removal from many pediatric vaccines, however it is still used in influenza, diphtheria and tetanus vaccines, blood products and many over-the-counter pharmaceuticals. The concentrations of thimerosal used by the UC Davis researchers were comparable to those attained in childhood vaccinations containing the preservative.

Researchers and parents have previously proposed links between childhood vaccines and autism, a neurodevelopmental disorder that affects language skills and social interactions. In addition to being a direct neurotoxicant, the UC Davis study indicates that thimerosal may also be an immunotoxicant, leaving the immune system vulnerable to microbes and other external influences.

“Our findings do not directly implicate thimerosal as a single causative agent for triggering neurodevelopmental disorders such as autism,” Pessah said. “There is growing evidence that autism is several disorders that we now refer to as just one. There is also growing evidence that some children with autism have unique immune cell composition and responses to antigens. The results of our work provide a framework to test the hypothesis that the genetic background of some individuals may render them especially susceptible to thimerosal.”

Other experts also advise drawing no final conclusions regarding thimerosal and autism based on these outcomes.

“These findings should be interpreted cautiously. Although they suggest that thimerosal may affect dendritic cell function, the pathophysiological consequences of thimerosal remain unclear,” said David A. Schwartz, a physician and director of the National Institute of Environmental Health Sciences.

Since cell functions can differ across organisms, Pessah will next study dendritic cells isolated from the blood of children with and without autism to confirm if the intercellular changes are the same in humans. The initial mouse study was funded by the National Institute of Environmental Health Sciences and the UC Davis M.I.N.D. Institute. Joining Pessah on the scientific team were molecular bioscientists Samuel R. Goth, Ruth A. Chu and Gennady Cherednichenko and pathologist Jeffrey P. Gregg.

A copy of “Uncoupling of ATP-mediated Calcium Signaling and Dysregulated IL-6 Secretion in Dendritic Cells by Nanomolar Thimerosal” can be downloaded at ehponline.org/docs/2006/8881/abstract.html.

The NIEHS-funded Center for Children’s Environmental Health and Disease Prevention is a multi-disciplinary research organization established to examine how toxic chemicals may influence the development of autism in children. The center’s goal is to contribute knowledge about autism that will lead to new prevention and treatment strategies. For more information, visit www.vetmed.ucdavis.edu/cceh.

The UC Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute is a unique collaborative center bringing together parents, scientists, clinicians and educators for research on autism and other neurodevelopmental disorders.

For more information, visit mindinstitute.org.

ehponline.org

New Hypertension Guidelines Fail To Improve Blood Pressure Control In People With Diabetes

Despite the publication of increasingly aggressive guidelines for lowering blood pressure in people with diabetes, this condition remains substantially unimproved, according to a study being published in the January issue of Diabetes Care.

A separate study being published in the same issue finds that small pupil size during adolescence may help predict diabetes-related complications later in life, such as retinopathy and microalbuminuria, a marker for both cardiovascular and kidney disease. The January issue of Diabetes Care also includes the American Diabetes Association’s (ADA’s) new Clinical Practice Recommendations, which are revised on an annual basis.

Hypertension Guideline Changes Fail to Improve Control

The blood pressure study, which compared hypertension control in people with and without diabetes from 1995-2005, showed that reducing blood pressure goals twice for people with diabetes during the past decade did little to improve control of this condition. The findings are consistent with other recent studies which showed that doctors fail to aggressively treat high blood pressure in people with diabetes, despite the fact that hypertension is a major symptom of cardiovascular disease, the leading killer of people with diabetes.

In 1997, and again in 2003, the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC) lowered blood pressure goals for people with diabetes. They currently recommend that people with diabetes keep blood pressure at or below 130/80 mmHg.

The changes, however, “did not lead to substantially better hypertension control for diabetics compared with non-diabetic patients,” the researchers concluded. “This finding is somewhat surprising considering the recognition of JNC guidelines as the gold standard for hypertension treatment, similar recommendations from other organizations such as American Diabetes Association, American College of Physicians, and American Academy of Family Physicians, and public health efforts to promote comprehensive diabetes care.”

Previous studies have shown that doctors intensified treatment of high blood pressure during as few as 12 percent of office visits when people with diabetes presented with this problem. High blood pressure can be treated through lifestyle and dietary changes as well as with numerous medications. Many people with diabetes also exhibit high blood pressure, an early warning sign for the development of heart disease.

Identifying effective interventions to deal with the challenge of lowering blood pressure in people with diabetes should be a top priority for future research, the authors concluded.

Small Pupil Size Predicts Complications in Adolescents

In a separate study, researchers identified a predictive relationship between small pupil size in adolescents with type 1 diabetes and the presence of microalbuminuria and retinopathy 12 years later. Small pupil size has been used to predict mortality in adults with diabetes but has not often been used in adolescents.

This study, by researchers in Australia, found that adolescents with type 1 diabetes whose pupils were reduced in size were at higher risk for complications from their disease in their 20s. In particular, they were at greater risk for retinopathy – a progressive eye disease – and microalbuminuria, or the presence of small amounts of albumin in the urine, which indicate cardiovascular and kidney problems.

The researchers recommend further research to determine if improved glycemic control when pupil abnormalities first appear would improve the condition and lead to fewer complications.

Clinical Practice Recommendations Updated

The ADA’s Clinical Practice Recommendations have been updated to include new information about treatment and prevention that reflects the latest research. Changes have been made in numerous areas, including the management of hyperglycemia in type 2 diabetes; nutrition recommendations; and screening and treatment for children who have both type 1 diabetes and celiac disease.

Managing hyperglycemia can be a problem for many people with type 2 diabetes. The revised recommendations now include information from a Consensus Statement published by the ADA and the European Association for the Study of Diabetes (EASD), which advises early intervention with metformin in combination with lifestyle changes to improve glycemic control. It also advises early initiation of insulin for those who present with weight loss and more severe symptoms.

In 2006, the ADA published Medical Nutrition Therapy (MNT) guidelines for people with diabetes, specific to individual populations, such as those who are obese or pregnant. The Clinical Practice Recommendations have been updated to reflect these guidelines and to encourage people with diabetes or pre- diabetes to seek individualized MNT to help them achieve their treatment goals.

Information about how to treat children who are diagnosed with both type 1 diabetes and celiac disease was also added to the Clinical Practice Recommendations this year. Up to 16 percent of children with type 1 diabetes are also diagnosed with celiac disease, an immune disorder that affects the digestive system, damages the small intestine and interferes with the absorption of nutrients from food. The recommendations call for more aggressive screening for celiac disease in children with type 1 diabetes who present symptoms such as weight loss, growth failure, abdominal pain and chronic fatigue. A gluten-free diet is recommended for those who test positive for celiac.

Diabetes Care, published by the American Diabetes Association, is the leading peer-reviewed journal of clinical research into the nation’s fifth leading cause of death by disease. Diabetes also is a leading cause of heart disease and stroke, as well as the leading cause of adult blindness, kidney failure, and non-traumatic amputations. For more information about diabetes, visit the American Diabetes Association Web site http://www.diabetes.org/ or call 1-800-DIABETES (1-800-342-2383).

American Diabetes Association
http://www.diabetes.org/

Updated Analysis Demonstrates Long-Term Survival Benefit Of EFAPROXYN(TM) In Treating NSCLC Patients Receiving Sequential Chemoradiotherapy

Allos Therapeutics, Inc. (Nasdaq: ALTH) today announced the presentation of updated results from its Phase 2 multi-center study of EFAPROXYN (efaproxiral) in patients with unresectable non-small cell lung cancer (NSCLC) receiving sequential chemoradiotherapy (S-CRT). Hak Choy, M.D, Professor and Chairman, Department of Radiation Oncology, University of Texas Southwestern Medical Center, and the study’s lead investigator, presented the findings in an oral presentation today at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology.

Dr. Choy and colleagues compared the safety and efficacy of EFAPROXYN when administered with S-CRT in patients with unresectable NSCLC compared to data from a Phase 3, Radiation Therapy Oncology Group (RTOG) 94-10 study. Results of a 5-year survival analysis indicated that patients in the EFAPROXYN study exhibited superior survival to patients with similar characteristics in the RTOG 94-10 study. Median survival of patients treated in the EFAPROXYN study was 20.6 months as compared to a median survival of 13.3 months for matched cases in the S-CRT arm of the RTOG 94-10 study and 16.9 months in the concurrent chemoradiotherapy (C-CRT) arm of the RTOG 94-10 study. The Kaplan- Meier estimates of 5-year survival rates for matched cases were 19% in the EFAPROXYN study and 10% in both the S-CRT and C-CRT arms of the RTOG 94-10 study. A portion of these data previously were reported at the 2003 World Conference on Lung Cancer and the 2003 Federation of European Cancer Societies.

Allos is currently conducting a Phase 1 study of EFAPROXYN in patients with locally advanced, unresectable (Stage III) NSCLC receiving C-CRT. Upon completion of this trial, the Company will determine its future development plans for EFAPROXYN in patients with Stage III NSCLC receiving a combined chemoradiotherapy regimen.

“These findings demonstrate the potential of EFAPROXYN to improve long- term survival rates of locally advanced NSCLC patients receiving sequential chemoradiotherapy,” said Michael E. Saunders, M.D., Allos’ Vice President, Clinical Development. “Upon completion of the on-going Phase 1 study of patients with Stage III NSCLC receiving concurrent chemoradiotherapy, we believe we will be positioned to further develop EFAPROXYN plus chemoradiotherapy under either accepted treatment regimen in this patient population.”

Study Design

This Phase 2, non-randomized, open-label, multi-center study was designed to assess the efficacy and safety of EFAPROXYN as a radiation sensitizer when administered with thoracic radiation therapy, following induction chemotherapy, for the treatment of patients with unresectable non-small cell lung cancer. Fifty-two previously untreated patients with NSCLC were enrolled at 13 sites. Treatment consisted of paclitaxel (225 mg/m2 on day 1) and carboplatin (AUC = 6 on day 1), 3 weeks apart, followed by thoracic radiation therapy (64 Gy/32 fractions/6-7 weeks) with concurrent EFAPROXYN (50 – 100 mg/kg). Results were compared to data from the Radiation Therapy Oncology Group study 94-10 in a case-matched comparison.

About Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases reported in the United States, occurring in approximately 160,000 patients per year. Approximately 25% – 40% of these patients are diagnosed with Stage III disease, of which half will receive chemoradiotherapy in the first line setting.

About EFAPROXYN

EFAPROXYN(TM) is the first synthetic small molecule designed to sensitize hypoxic, or oxygen-deprived, areas of tumors during radiation therapy by facilitating the release of oxygen from hemoglobin, the oxygen-carrying protein contained within red blood cells, and increasing the level of oxygen in tumors. The presence of oxygen in tumors is an essential element for the effectiveness of radiation therapy. By increasing tumor oxygenation, Allos believes that EFAPROXYN has the potential to enhance the efficacy of standard radiation therapy.

About Allos Therapeutics, Inc.

Allos Therapeutics, Inc. (ALTH) is a biopharmaceutical company focused on the development and commercialization of small molecule therapeutics for the treatment of cancer. The Company has two product candidates in late-stage clinical development: EFAPROXYN (efaproxiral), a radiation sensitizer currently under evaluation in a pivotal Phase 3 trial in women with brain metastases originating from breast cancer, and PDX (pralatrexate), a novel, next generation antifolate currently under evaluation in a pivotal Phase 2 trial in patients with relapsed or refractory peripheral T-cell lymphoma. The Company is also evaluating RH1, a targeted chemotherapeutic agent, in a Phase 1 trial in patients with advanced solid tumors. For additional information, please visit the Company’s website at http://www.allos.com.

Safe Harbor Statement

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements concerning the potential safety and efficacy of EFAPROXYN for the treatment of NSCLC patients receiving S-CRT or C-CRT; the Company’s future development plans for EFAPROXYN for the treatment of NSCLC patients receiving S-CRT or C- CRT; and other statements that are other than statements of historical facts. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expects,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “continue,” and other similar terminology or the negative of these terms, but their absence does not mean that a particular statement is not forward-looking. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties include, among others: that clinical trials may not demonstrate the safety and efficacy of EFAPROXYN for the treatment of NSCLC patients receiving S-CRT or C-CRT; that the Company may experience difficulties or delays in its clinical trials, whether caused by adverse events, investigative site initiation rates, patient enrollment rates, regulatory issues or other factors; that the Company may be unable to obtain the regulatory approvals necessary to conduct additional clinical trials; that data from preclinical studies and clinical trials may not necessarily be indicative of future clinical trial results; and the risk that the Company may lack the financial resources and access to capital to fund future clinical trials for EFAPROXYN or any of its other product candidates. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the “Risk Factors” section of the Company’s Annual Report on Form 10-K for the year ended December 31, 2005, and in the Company’s other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward- looking statements to reflect events or circumstances after the date of this presentation, except as required by law.

Allos Therapeutics, Inc.
http://www.allos.com

Do You Have Concerns About Asthma Treatments?

Asthma UK is seeking help from people with asthma in identifying the most common concerns they have about their treatments, in order to help prioritise research.

This work is a partnership between Asthma UK, the British Thoracic Society and the James Lind Alliance. The aim is for people with asthma and clinicians to agree priority areas of research about asthma treatments.

In order to build a better understanding of the most common concerns, we are asking people with asthma and parents/carers of children with asthma to fill in a short survey about their unanswered questions.

Your questions

Do you have a question about an asthma treatment you have experienced for which you have not been able to find an answer? Do you have concerns about the effects of a treatment, that you would like a doctor or asthma researcher to explore? Are there areas of research you feel a scientist should look into? Are there alternative or better ways of treating asthma you would like us to consider? Tell us in the survey.

‘It is important for people with asthma to tell us about their concerns, questions or uncertainties’, said Jenny Versnel, Asthma UK’s Assistant Director, Research. ‘Their ideas will help us to identify and prioritise important questions about the effects of treatments, and help future asthma research to address them.’

Fill in the survey

To participate in the short survey, please follow the links below. This survey runs until 27 March 2006. Your responses will be anonymous and any information you provide will help us to build a general understanding of the questions about asthma treatments we have yet to find answers for. We will therefore not be able to respond to your questions, but if you have a particular concern about your asthma please contact your GP or the Asthma UK Adviceline. You will be able to keep updated with the progress of this project later in the year.

— Fill in the survey for adults with asthma

— Fill in the survey for parents of children with asthma

— British Thoracic Society — James Lind Alliance

Call the Asthma UK Adviceline for advice and information about asthma treatments – 08457 01 02 03, 9am-5pm, Monday-Friday. Email your query online now.

http://www.asthma.org.uk

Study Identifies Glucose ’sensor’ That Plays Dual Role In Glucose Metabolism And Fat Synthesis

In the study, glucose is shown to stimulate the activity of the Liver X Receptors (LXR) a and b, The LXRs act as sensors of dietary components, orchestrating the body’s response to nutrients such as oxysterols (short-lived derivatives of cholesterol) and controlling gene expression linked to cholesterol and fat metabolism.

“When you eat, glucose pours into the gut and is recognized by LXR in the liver, which then activates expression of the enzymes that turn excess glucose into triglycerides that are stored as fat,” said Enrique Saez, a Scripps Research scientist who led the study. “The fact that our study demonstrates that LXR does both-it binds to glucose and it induces fatty acid synthesis-is significant and makes LXR a potential target for diabetes and obesity treatments.”

In some recent animal studies, Saez pointed out, activation of LXRs using synthetic molecules also induced regression of atherosclerosis, the clogging, narrowing, and hardening of the body’s large arteries and blood vessels that can lead to stroke, heart attack, and eye and kidney problems. Elevated levels of pathogenic cholesterols, also known to bind LXR, are a primary risk for development of atherosclerosis.

“The integration of glucose sensing and control of lipogenesis by LXR may explain why low-fat/high-carbohydrate diets induce hypertriglyceridemia [an elevated level of triglycerides in the blood],” Saez said. “LXR can sense surplus glucose, induce fatty acid synthesis, and prompt the liver’s export of triglycerides into the bloodstream. Since LXR acts as the body’s sensor of a buildup of pathogenic cholesterol, its ability to bind both glucose and oxysterols suggests that LXR may be a link between hyperglycemia and atherosclerosis.”

In fact, Saez and his colleagues originally looked at LXR as a drug target for atherosclerosis. But when they fed synthetic LXR ligands to mice to induce activation, they discovered that the mice metabolized glucose more effectively and that activation suppressed new production of glucose in the liver.

That prompted the scientists to look more closely at glucose levels as the LXR activating mechanism in the liver.

To their surprise, what Saez and his colleagues discovered was that glucose bound directly to LXR. This was unexpected because the carbohydrate does not conform to the standard definition of a typical ligand that activates nuclear receptors, transcription factors that coordinate gene expression in response to hormonal and environmental signals. This discovery, Saez said, represents the first signaling pathway where a carbohydrate activates a nuclear receptor, although the precise mode of binding remains unknown.

As part of the study, mice were put on exclusive sucrose or D-glucose diets; all diets were devoid of cholesterol to minimize naturally occurring oxysterols. D-glucose and GW3965 (a synthetic LXR activator) induced similar changes in hepatic gene expression, indicating that LXR functions as a glucose sensor in vivo that responds to increasing liver glucose uptake. The ability of the LXRs to respond to glucose and its derivatives was very specific: no effect was seen in other nuclear receptors tested.

The current study focused primarily on the role of glucose sensing in the liver and gut. New studies will focus on the question of whether glucose levels in other tissue types, such as the pancreas, activate LXR, Saez added.

The study was published December 20 in an advanced, online edition of the journal Nature.

Other authors of the study, The Nuclear Receptor LXR is a Glucose Sensor, include Nico Mitro of The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation; and Puiying A. Mak, Leo Vargas, Cristina Godio, Eric Hampton, Valentina Molteni, and Andreas Kreusch of the Genomics Institute of the Novartis Research Foundation.

The study was supported by the Genomics Institute of the Novartis Research Foundation.

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.

Written by: Keith McKeown
Scripps Research Institute
www.scripps.edu

Radiation After Surgery Doubles Survival Time For Some Lung Cancer Patients

Patients with lung cancer that has spread to mediastinal lymph nodes – located between the chest, breastbone and spine – who receive radiation after surgery and chemotherapy live twice as long as patients who do not receive radiation after surgery, according to a study presented at the plenary session November 6, 2006, at the American Society for Therapeutic Radiology and Oncology’s 48th Annual Meeting in Philadelphia.

The study was part of a larger randomized study, ANITA 1, which examined the effectiveness of chemotherapy after surgery in 840 non-small cell lung cancer patients and found that additional chemotherapy after surgery improves overall survival in cancer that has spread to the lymph nodes. In this study, radiation was not randomized nor mandatory but only recommended for patients whose disease had spread to the lymph nodes. 232 lung cancer patients received radiation after undergoing surgery to remove their tumor with or without chemotherapy.

Researchers found that additional radiation after chemotherapy benefited patients whose cancer had spread to mediastinal lymph nodes. At that stage, those who underwent chemotherapy and radiation after surgery lived almost two years longer (47 versus 24 months) than those patients who had only chemotherapy after surgery. “This is the first time that a clinical trial has examined the effectiveness of radiation after surgery for lung cancer,” said Jean-Yves Douillard, M.D., Ph.D., lead author of the study and a medical oncologist at the Centre Rene Gauducheau in St Herblain, France. “The results show that radiation treatment should be considered for resected non-small cell lung cancer with involved mediastinal lymph nodes in addition to chemotherapy. The data observed in this study, however, needs to be confirmed in a prospective randomized trial of radiation, in addition to chemotherapy.”

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For more information on radiation therapy for lung cancer, visit http://www.rtanswers.org/.

The abstract, “Impact of Radiation on Survival After Complete Resection of Non-small Cell Lung Cancer: Descriptive Analysis In the Randomized Adjuvant Chemotherapy Trial Anita 1,” was presented at the plenary session on Monday, November 6.

Contact: Beth Bukata
American Society for Therapeutic Radiology and Oncology