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    November 24, 2011 at 2:24 pm

    Risk Model Developed to Recommend How Often Women Should have Mammograms
    By Medimaging International staff writers
    While most women already undergo mammograms to help detect breast cancer, there has been significant controversy about how frequently women need to be screened. To help answer that question, researchers are developing a customized risk model to recommend how often a woman should have a mammogram based on her unique risk factors.

    “This could change how we provide breast care,” said Jennifer Harvey, MD, professor of radiology at the University of Virginia (UVA) School of Medicine (Charlottesville, USA). “Women will have personalized knowledge to make decisions about getting screened.”

    Dr. Harvey and William Knaus, MD, professor of public health sciences, were part of a research team that recently received a USD 5.5 million grant from the US Department of Defense Congressionally Directed Medical Research Programs to fund the initial phase of a study to develop the risk model.

    While recommendations for breast cancer screenings are now “one-size-fits-all” largely based on a woman’s age, Dr. Harvey noted, the new risk model could generate very different recommendations for women of the same age. Lower-risk women may be advised to undergo a breast cancer screening every other year, whereas women at higher risk may be recommended to have more frequent screenings with more sensitive equipment such as magnetic resonance imaging (MRI).

    The risk model will combine medical data with guidance from women on how they would like to approach screenings for breast cancer. Existing risk models are largely based on a woman’s personal or family history of cancer; UVA’s risk model will add breast density, which is one of the strongest indicators of a woman’s breast cancer risk.

    As part of the study, Drs. Harvey and Knaus will work with Martin Yaffe, MSc, PhD, a senior scientist at Sunnybrook Health Sciences Center (Toronto, Canada) to determine which of two methods is best for rapidly measuring breast density using digital mammograms.

    To complete the risk model, a series of phone surveys and focus groups will collect data from women about their perspectives on screening for breast cancer. “Some women have concerns about the radiation exposure from mammograms, while other women may want to take a more aggressive approach to screening,” Dr. Knaus stated.

    Drs. Harvey and Knaus plan to spend the next three years developing and corroborating the screening model at UVA before testing it through a US study; if successful, the model could be available for widespread use in five to six years.

    Therapy For Radiation Sickness said:
    November 24, 2011 at 5:56 am

    A combination of two drugs may alleviate radiation sickness in people who have been exposed to high levels of radiation, even when the therapy is given a day after the exposure occurred, according to a study led by scientists from Dana-Farber Cancer Institute and Children’s Hospital Boston.

    Mouse studies of other potential therapies suggest they would be effective in humans only if administered within a few minutes or hours of radiation exposure, making them impractical for use in response to events involving mass casualties. In contrast, the larger time window for administering the two-drug regimen raises the prospect that it could become a mainstay of the response to public health threats such as a nuclear power plant accident or nuclear terror attack.

    In a paper published online by the journal Science Translational Medicine, the scientists report the beneficial effects, in mice, of a combination of a fluoroquinolone antibiotic (similar to the commonly used human antibiotic ciprofloxacin, or “Cipro”) and a synthetic version of the natural human infection-fighting protein BPI. Mice that received the combination a day after being exposed to high doses of radiation fared far better than mice that received neither or only one of the agents. Whereas radiation exposures of that magnitude almost always prove fatal within a month, 80 percent of the mice that received the two agents were alive and apparently healthy a month into the study.

    The study’s lead author is Eva Guinan, MD, of Dana-Farber, and the senior author is Ofer Levy, MD, PhD, of Children’s Hospital Boston.

    The investigators also found that the ability to generate new blood cells which can shut down in the aftermath of radiation exposure rebounded much more quickly and vigorously in the mice treated with fluoroquinolone and rBPI21 (the synthetic version of BPI), potentially contributing to their return to health.

    “Both fluoroquinolone antibiotics and rBPI21 have been shown to be quite safe in humans,” says Levy. “Their combined effectiveness in our study involving mice is an indication that they may be equally beneficial in people.”

    The research potentially represents a major step in the United States government’s efforts to build a stockpile of therapies to counter radiological dangers.

    “There is great interest in creating systems for dealing with the short- and long-term health risks of a significant release of radiation, whether from an accident at a nuclear power plant, an act of terrorism, or even a small-scale incident in which a CT machine malfunctions,” says Guinan.

    “Developing useful agents has proven difficult. Most existing drugs aren’t effective enough and must be given within a very short time frame to provide any benefit. The recent disaster at the Fukushima nuclear power plant in Japan illustrates the need for agents that can be deployed rapidly to treat large populations.”
    Radiation sickness, also known as acute radiation syndrome, varies with the amount of radiation an individual receives. The first signs of the disease usually are nausea and vomiting, which can be followed by fever, dizziness, weakness, bloody vomit and stools, difficulty breathing, and infection. The body’s blood-making tissue, nervous system, digestive tract, lungs, and cardiovascular system all can be affected. At very high doses, radiation is usually fatal.

    Within the body, the effects of heavy radiation may include leakage of bacteria and the toxins they produce into the bloodstream from the digestive tract or through broken skin. Radiation effects play havoc with the function of the heart and lungs, disrupt the process of blood coagulation, and inflame tissue throughout the body.

    When bacteria or certain toxins enter the blood under normal conditions, the body’s immune system responds by dispatching neutrophils white blood cells to destroy the intruders. The neutrophils release a payload of BPI (bactericidal/permeability-increasing protein), which sticks tightly to molecules called endotoxins on the surface of the bacteria. The binding not only helps BPI kill the bacteria but also blocks inflammation caused by live or dead bacteria something that conventional antibiotics do not do.

    When a person is exposed to high levels of radiation, however, the ability to generate neutrophils is almost obliterated. “It’s a perfect storm of disease-causing events,” Guinan remarks. “Radiation results in bacteria and endotoxins entering the bloodstream at the same time that the body’s defenses are lowered.”

    The treatment approach developed by Guinan, Levy and their colleagues takes direct aim at two potential contributors to radiation sickness: bacteria and the endotoxins on their surface. “We theorized that a two-drug therapy would be most effective,” Levy states. “Others had already shown some benefit to treatment with fluoroquinolones after radiation; at least part of the benefit came from killing bacteria in the blood. The second, rBPI21, would bind to, neutralize, and ‘mop up’ the endotoxins released by the dying bacteria, thereby removing the trigger of the inflammation process.”

    In the study, researchers exposed mice to radiation levels of 7 gray (by comparison, the amount emitted by a standard X-ray machine is 0.01 grays.) At those levels, radiation is 95 percent lethal to mice within 30 days.

    Twenty-four hours after the radiation exposure, researchers began treating some of the mice with daily doses of fluoroquinolone antibiotic, some with twice-daily doses of rBPI21, and some with both. The mice that received both agents not only had much higher survival rates than the others, but their ability to generate new blood cells also recovered much more quickly.

    The promise of this approach is underscored by the nature of the two agents, the study authors say. Both have a proven safety record in humans and can be stored for long periods of time, making them suitable for stockpiling.

    The use of rBPI21 was inspired by research in patients whose blood-making tissue undergoes changes similar to those of people exposed to high levels of radiation: cancer patients who undergo bone marrow or stem cell transplants. Such transplants involve high doses of chemotherapy and in some cases radiation therapy, which kills cancer cells but also destroys the blood-forming tissue of the bone marrow, followed by an injection of stem cells to rebuild the blood supply.

    “We measured BPI levels in patients receiving stem cell transplants and found they were BPI deficient while also having bacterial endotoxin in their bloodstream,” says Levy, who first studied BPI as a graduate student at New York University with the protein’s discoverers, Peter Elsbach, MD, PhD, and Jerrold Weiss, PhD. “These observations led to the hypothesis that replenishing BPI could decrease the toxicity of radiation,” Levy adds.

    The current study is the product of five years of work and collaboration between Levy, Guinan and their associates. “My experience in the field of stem cell transplantation, including the use of total-body irradiation, and caring for patients with diseases of the bone marrow has been a perfect complement to Ofer’s expertise in neutrophil function and innate immunity [the arm of the immune system that is the first line of defense against infection],” Guinan comments. “This result is a promising new strategy for response to a nuclear event.”

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