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Anal Pap Smear Could Save Lives—and CheaplyIn the history of cancer medicine, few discoveries have been more celebrated than the Pap smear. Since its use in the 1960s, this simple and inexpensive screening test has led to a dramatic drop in cervical cancer in women. According to a new study by researchers at the Harvard School of Public Health and the University of California at San Francisco, the Pap smear could inspire a second success story, this time among gay and bisexual men who suffer higher than average rates of anal cancer. The study, published in the June 1 issue of The American Journal of Medicine, suggests that widespread use of a similar screening technique would allow detection—and early removal—of pre-cancerous anal lesions among high-risk HIV negative men. "We think immediate steps should be taken to identify real-world barriers to such a screening program," says lead author Sue Goldie, assistant professor of health decision science at HSPH. Anal cancer currently affects as many as 35 American gay men per 100,000 per year—a figure comparable to the 40 women per 100,000 who contracted cervical cancer in the U.S. before the use of Pap smears. Like cervical cancer, anal cancer is caused by a sexually transmitted virus, human papillomavirus (HPV), and can be detected by the same test. Using epidemiological data from San Francisco and Seattle, Goldie and her colleagues created a model to ascertain the clinical benefits and the cost effectiveness of anal cancer screening in HIV-negative gay and bisexual men. They found that life-expectancy benefits were the same as or greater than for the cervical Pap smear, and at a comparably low cost. A study published last year by Goldie and her colleagues showed that anal screening would also be beneficial for HIV-positive men but on a more frequent basis—every year as opposed to every two to three years for HIV-negative men. Because of the simplicity of the procedure—a simple swab—large scale screening programs, once approved, could be implemented with relative ease. Before such screening programs are actually put into place, the researchers plan to expand their study to include cities other than San Francisco and Seattle to dismiss the possibility that the disease pattern in these cities is unique. Two Wrongs Make a Right as One Infection Stops AnotherFor years, scientists have wrangled with one of the great conundrums of medicine: why do some people when infected with a germ develop disease while others with the same bug remain healthy? Helicobacter pylori infects nearly 50 percent of people and yet only a fraction of them develop disease—ulcers and gastric cancer. Even more puzzling, those affected tend to reside in geographic clusters. "You can go from one part of the world to another and find big differences in rates of gastric cancer," says Cathryn Nagler-Anderson, HMS assistant professor of pediatrics (immunology) at Massachusetts General Hospital. She, Hai Ning Shi, HMS instructor in pediatrics at MGH, and colleagues at HMS and MIT have proposed a novel solution to this enigma. In the May Nature Medicine, they argue that those who remain immune from cancer may be carrying an unlikely ally: other bugs. These bugs subvert the normal immune response, which prevents cancer from developing. The proposal derives from an intriguing experiment conducted by the researchers. Normal mice, when infected with H. pylori, often develop precancerous gastric lesions. But the researchers found that when they infected the mice first with hel-minthic parasites, the animals remained relatively free of the cancer precursors. As for how the helminths might be subverting disease, the researchers believe they may cross molecular signals. When Helicobacter mounts an infection, the immune system calls upon one branch of the T cell army, Type 1 helper T cells, which appear to be involved in provoking cancer. But the helminths rally another branch, Type 2 helper T cells. Mice infected with both pathogens exhibited the helminth-type, or Type 2, immune reaction, which appears not to provoke cancer. But there is another bugging question: helminths infect most people. Why then do they protect some populations and not others? "We can only speculate that in different areas of the world, different sorts of helminths can have different effects," says Nagler-Anderson. Combination Diet Cuts Blood Pressure"Hold the salt," should be the motto of all Americans seeking to lower their blood pressure, whether or not they suffer from hypertension. To reap even lower blood pressure readings, people should also say no to red meat and sugar. The findings derive from a study presented on May 17 at the American Society of Hypertension annual meeting in New York City. Researchers at Brigham and Women's Hospital, working in collaboration with scientists at other institutions, enrolled 412 subjects, with and without hypertension, on one of two diets. The two dietary plans were a typical U.S. diet and a diet rich in fruits, vegetables, and low-fat dairy products and low in red meat and sugar. Subjects followed their diets at three sodium levels. The three sodium levels, consumed for four weeks at a time, were a high intake of 3.3 grams daily, an intermediate intake of 2.4 grams, and a low intake of 1.5 grams. Subjects on both plans exhibited lowered blood pressure when following the low sodium regime. But those on the fruit-and-vegetable-rich diet displayed the greatest reduction during the four-week low sodium period. The combination reduced blood pressure more than either the diet or lower sodium intake alone—regardless of whether the subject had hypertension to begin with. "The medical community has long debated which dietary factors play the most crucial role controlling hypertension," says senior study author Frank Sacks, HMS associate professor of medicine. "Now there is clear evidence that shows a diet that emphasizes fruits and vegetables and low-fat dairy products combined with low salt intake is optimal for lowering blood pressure and controlling hypertension." Technique Turns Down Gene SilencingGene silencing, which involves complete transcriptional repression of particular genetic segments, poses a significant obstacle to gene therapy. Working with the beta-globin gene, which encodes a protein necessary for normal red blood cell function, a collaboration of researchers from HMS, MIT, and other institutions has developed a technique that can largely overcome this genetic challenge. The findings, published in the May 9 PNAS, build from previous work conducted by senior author Philippe Leboulch, HMS assistant professor of medicine at Brigham and Women's Hospital and MIT, and his colleagues. When new genetic information is introduced into stem cells in the bone marrow, it tends to remain inactive. Even when genes are not initially silenced, progressive loss of expression of the transferred gene is often observed. To overcome these challenges, Leboulch and his colleagues manipulated the retroviral beta-globin vector so it also contained the genetic information for a marker protein and a portion of the DNA that acts as an enhancer for the beta-globin gene. They also introduced a specific promoter sequence to the vector. When only the cells that expressed the marker protein were selected for transplantation, each of seven lethally irradiated mice that received bone marrow transplants expressed the donor beta-globin protein in 20 to 95 percent of their red blood cells at levels that persisted for at least nine and a half months post-transplantation. Similar results were obtained when bone marrow from three primary recipients was transplanted into secondary hosts. The transferred beta-globin gene remained expressed at lower than ideal levels on a per-cell basis, however. The researchers speculate that inclusion of a larger portion of the enhancer region for the globin gene may be able to counteract this problem. Ultimately, these techniques may improve treatments for globin disorders like thalassemia and sickle cell disease as well as other conditions. —Catherine Chu |
