STUDY: Surprising finding may explain HIV’s hold on the body

JOURNAL: Institut Cochin

AUTHORS: France Pietri-Rouxel

ABSTRACT: The AIDS virus, long known to infect immune system cells, also takes up residence in fat cells, French researchers report. They found HIV in the fat tissue of patients with irregular fat deposits known as lipodystrophies — a side-effect of long-term drug treatment for the virus.

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COMMENTARY: THE FINDING could help explain why HIV has proven impossible to eradicate, and it may open a whole new window in understanding how the fatal and incurable virus works.

France Pietri-Rouxel of the Institut Cochin in Paris and colleagues stumbled upon the finding by accident, when she was treating HIV patients whose body fat began to redistribute itself in odd ways — the condition known as lipodystrophy.

A specialist in fat tissue, she was removing fat from the abdomens of the patients and injecting it into their cheeks to fill out their faces. “The thin, gaunt face is one of the disturbing signs of an HIV patient,” she said in an interview.

Jacques Leibowich of Hopital Foch in Suresnes, France, asked her for samples of the fat tissue for an unrelated study he was doing. To his surprise, HIV DNA turned up in the tissue. T

The human immunodeficiency virus, discovered 20 years ago, is known to infect immune system cells. It favors CD4 T-cells, lymphocytes that respond to a viral infection.

The virus grapples the cells, injects its genetic material and forces the cell to manufacture more copies of itself.



To do this it uses receptors, a kind of molecular doorway into the cell. The two main receptors HIV uses are called CD4 and CCR5 — both found on T-cells.

But fat cells also have CCR5 receptors, and now it appears HIV must use these to infect fat cells.

Robert Gallo, head of the Institute and one of the men who discovered HIV, said the finding could help explain why HIV lurks in the body for years despite treatment with drugs that can suppress its activity. Experts believe it must lie low in a pool of cells known as a reservoir.

“That could be a major contributor to the reservoir,” Gallo said. “It could also be the reason that some people with HIV lose fat.”

Pietri-Rouxel said all seven patients she treated had HIV in their fat. All were taking drug cocktails known as highly active antiretroviral treatment or HAART, which had reduced the virus in their body to levels that cannot be detected in blood tests.

“What we don’t know is the relationship between the treatment and the infected cells,” Pietri-Rouxel said.

“Could the treatment have caused it?” asked Leibowich.

Pietri-Rouxel said there was some evidence the virus was acting as it does in other cells and using them as little factories to make copies of itself, but this was not yet certain.

If all fat cells in an HIV patient are infected, the implications could be serious, Leibowich said. “A person has about a kilogram (2 pounds) of lymphocytes,” he said. “But someone like me has 15 kilograms (30 pounds) of fat. So fat cells could be the more important source.”

The researchers now plan to look for infected fat cells in other HIV patients, especially those who have not developed lipodystrophies.

STUDY: Cancer Burden is Expected to Rise with an Aging Population

JOURNAL: Cancer

AUTHORS: Brenda K. Edwards, Ph.D.

ABSTRACT: New data for 1999 show that death rates for all cancers combined continued to decline in the United States. However, the number of cancer cases can be expected to increase because of the growth and aging of the population in coming decades, according to a report released in the "Annual Report to the Nation on the Status of Cancer, 1973-1999, Featuring Implications of Age and Aging on the U.S. Cancer Burden".

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COMMENTARY: The report is by the National Cancer Institute (NCI); the American Cancer Society (ACS); the North American Association of Central Cancer Registries (NAACCR); the National Institute on Aging (NIA); and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS) and the National Center for Chronic Disease Prevention and Health Promotion.

The initial Report to the Nation, issued four years ago, documented the first sustained decline in cancer death rates. This trend was a notable reversal from increases that had been seen since the 1930s, which was the period when record keeping on deaths first included the entire nation. "The continuing decline in the rate of cancer deaths once again affirms the progress we've made against cancer, but the report also highlights the need for an acceleration of research as the population of the United States ages," said NCI Director Andrew C. von Eschenbach, M.D.

Lung cancer is still the leading cause of cancer death in the United States. During the most recent reporting period, it accounted for almost one-third of cancer deaths in men and about one-fourth of cancer deaths in women. Colorectal cancer is the second leading cause of cancer death, followed by breast and prostate cancer.

"The good news in this report is the continuing fall in cancer death rates by slightly more than one percent per year between 1993 and 1999," said John R. Seffrin, Ph.D., chief executive officer of the American Cancer Society. "Of special note is the continuing decline in death rates for the four most common cancers."

STUDY: NSAIDs may fight pancreatic cancer

JOURNAL: J Natl Cancer Inst. 2002;94:1168-1171

AUTHORS: Kristin E. Anderson, PhD

ABSTRACT: Regular aspirin use among postmenopausal women may reduce their risk of developing pancreatic cancer. Laboratory tests have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may fight pancreatic cancer, but until now there has been only limited evidence in humans to back up this theory.

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COMMENTARY: In this study, researchers looked at NSAID use among more than 28,000 postmenopausal women, from 1992 through 1999.

They found that women who reported any use of aspirin had a 43% lower risk of pancreatic cancer compared with women who never took aspirin. In addition, the more aspirin use a woman reported, the less likely she was to develop pancreatic cancer.

Other NSAIDs did not have the same effect. Use of NSAIDs other than aspirin did not decrease the risk of pancreatic cancer.

Study author Kristin E. Anderson, PhD, of the University of Minnesota in Minneapolis, and colleagues say NSAIDs are thought to help prevent pancreatic cancer by inhibiting a particular enzyme in the body, thereby reducing inflammation.

The researchers say that their study suggests the drugs may also work in other ways to fight cancer because only aspirin was found to have a protective effect. But, they add, the women in the study used aspirin more often than they did other NSAIDs. This may partially explain why there was a stronger association between aspirin use and cancer prevention than was seen with the newer NSAIDs.

The researchers say that if further studies confirm this link, "more than 40% of pancreatic cancers may be prevented by aspirin among people who don't normally take aspirin." Although experts are not exactly sure what puts a person at risk for pancreatic cancer, smoking and obesity are thought to increase the risk.

STUDY: A new exam may help detect ovarian cancer earlier and improve the chances of survival

JOURNAL: Journal of the National Cancer Institute

AUTHORS: Dr. Le-Ming Shih

ABSTRACT: Each year, more than 23,000 American women are diagnosed with ovarian cancer and about 14,000 die from the disease. Yet, while there are mammographies to test for breast cancer and colonoscopies for colon cancer, there is still no standard screening exam for early detection of ovarian cancer. But this might change soon.

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COMMENTARY: Doctors aren’t making such grand claims yet with this new test, but they are heralding the new possibilities this test offers in picking up the cancer faster and getting patients treated earlier. This new test is based on digital SNP (single-nucleotide polymorphisms) analysis, which can detect a genetic imbalance in patients. Typically, we inherit DNA from our parents in equal proportions, one copy from our mother and one copy from our father. But cancer patients develop multiple copies of one parent’s genetic markers and less of the other parent’s. It’s this imbalance that doctors can measure in blood samples and analyze with the specialized digital technology.

In this recent study, researchers were able to identify the imbalances in 87 percent of women with early-stage ovarian cancer and 95 percent of women with advanced disease. To make sure the test was specific for ovarian cancer, researchers collected blood samples from 31 cancer-free women. There were no genetic imbalances found in any of the healthy women—more support that this test could differentiate between those with cancer and those who are disease-free.

Dr. Le-Ming Shih, the lead researcher on the study, cautions that while these results are extremely encouraging, they are only preliminary. “This study is important, because it tells us that this technology can detect ovarian cancer early. Now we will do more studies to see if we can combine the test with others to achieve an even higher detection rate.” Shih added that one of the remaining concerns is cost. This new blood test could be expensive, costing as much as $350. The goal would be to get the test closer to $100.

For a long time, health advocates have pushed for more research dollars to find better ways to diagnose ovarian cancer earlier in women. With this digital SNP blood test, their efforts may pay off—and thousands of lives may be saved.

STUDY: Bextra has been associated with serious allergic reactions

JOURNAL: FDA and drugmaker Pharmacia

AUTHORS: FDA

ABSTRACT: The US Food and Drug Administration (FDA) and drugmaker Pharmacia are advising doctors that the firm's COX-2 inhibitor valdecoxib (Bextra) has been associated with serious allergic reactions and should not be prescribed to patients allergic to sulfa.

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COMMENTARY: In a notice issued on Friday, the FDA said it has received post-marketing reports regarding various allergic events, including skin and anaphylactoid reactions.

Although the events were rare, some patients required hospitalization, the FDA added.

The FDA said the Bextra label has been updated to reflect the new case reports and contraindication.

On November 13, according to the FDA, Pharmacia sent similar letters to healthcare professionals, advising them of the post-marketing reports and new warnings that will be included on the updated label.

In a copy of the letter posted on the agency's Web site, Pharmacia said these cases occurred in patients with and without a history of allergic-type reactions to sulfonamides and included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and erythema multiforme.

The company said the label would be updated to carry two separate warnings for the skin and anaphylactoid reactions, as well as a section to outline the post-marketing experience. According to the label included in the Pharmacia letter, an estimate of the frequency was not possible because the reactions were voluntarily reported from a population of uncertain size.