(Last updated 6:18 PM ET April 28)

NEW YORK, Apr 28 (Reuters Health)

-- For centuries, the Chinese herbal medicine called Danggui Longhui Wan has been used in the treatment of leukemia. In an article published this week in Nature Cell Biology, European researchers report that they have discovered that the active ingredient in the herbal remedy works by blocking the proliferation of cancer cells.

The team, led by Ralph Hoessel of the University of
Kaiserslautern in Germany, note that Danggui Longhui Wan includes 11 different herbal medicines. More than 30 years ago, researchers at the Chinese Academy of Medical Sciences identified the active ingredient in this complex mixture as Qing Dai, a dark blue powder prepared from various plants and containing a large amount of the blue dye indigo.

The leukemia-fighting ingredient was found to be indirubin, a red-colored relative of the indigo blue dye.

Hoessel's team believes that indirubin stops the uncontrolled growth of tumor cells by inactivating enzymes called cyclin-dependent kinases that govern cell division.

When indirubin binds to these enzymes, it blocks their
activity and halts cell division, thus stopping the proliferation of cancer cells.

The investigators note that indirubin has been approved for clinical trials in patients with chronic myelocytic and chronic granulocytic leukemia. One study found that "26% of the 314 chronic myelocytic leukemia patients showed complete remission and 33% showed partial remission in response to indirubin treatment. Toxicity was low and side effects were limited to mild abdominal pain, diarrhea, nausea and vomiting," they report.

Hoessel and colleagues plan to continue studying how
indirubin works. They conclude that this information may help to optimize the use of the agent in fighting cancer, and may suggest new avenues for cancer research.

SOURCE: Nature Cell Biology 1999;1:60-67.


SAN DIEGO (NYT Syndicate)

-- An extract from a Chinese herb may someday help overcome one of the biggest obstacles to treating lung cancer, according to preliminary study findings released here Sunday. Lung cancer can often resist treatment when a gene known as p53 mutates to thwart chemotherapy drugs.

A new class of tumor-fighting agents, based on an immune-system component called tumor necrosis factor (TNF), have shown promise in solving this problem because they kill cancer cells, regardless of what p53 does. TNF-related agents, however, are imperfect — sometimes toxic to normal cells or inefficient in knocking out cancerous ones. One newly discovered member of the TNF family, TNF-related apoptosis-inducing ligand (TRAIL), has proven to be less toxic to healthy cells; but TRAIL's clinical use has been hampered by the fact that it also activates a substance that impairs its ability to wipe out cancer cells.

Now, California researchers have found that a chemical derived from the Chinese herb Tripterygium wilfordii boosts TRAIL's cancer-killing capacity. Findings presented at the American Lung Association and the American Thoracic Society's joint annual meeting showed that the chemical, called triptolide, can also obliterate some types of lung-cancer cells on its own.

According to lead researcher Dr. Glenn Rosen, an assistant professor of pulmonary and critical care medicine at Stanford University, some tumor cells are susceptible to triptolide, and others succumb to a combination of TRAIL and the herb product. In experiments on two types of lung-cancer cells, Rosen's team found that while TRAIL alone killed just 30 percent of tumor cells, the combination of TRAIL and triptolide destroyed 80 percent to 95 percent. Triptolide, used in China to treat arthritis, apparently "sensitizes" tumor cells to go along with TRAIL, which itself acts by encouraging cells to destroy themselves. The Stanford researchers reported that triptolide might have a future role in chemotherapy for lung cancer and other types of tumors. Copyright 1999 The New York Times Syndicate. All rights reserved.


Health News for April 21, 1999

By Ann Quigley

NEW YORK, Apr 21 (Reuters Health) --

-- Endometriosis, a disease that affects women in their reproductive years, may be linked to an increased risk of cancers such as malignant melanoma, breast and ovarian cancers in patients and their families, according to preliminary research presented at a press conference in Manhattan on Wednesday.

"Endometriosis may well be a lot more serious that people have thought, and because of that we all need to keep our antennae up," Mary Lou Ballweg, president of the Endometriosis Association, told Reuters Health. "If it is serious, we need to be diagnosing it better. We can't be telling these women for years on end that it's in their heads, or it will be better when they have a baby, which is what women typically were told."

In addition to presenting study data, Ballweg also announced launch of the Milwaukee, Wisconsin-based Association's research initiative in partnership with Vanderbilt University, in Nashville, Tennessee. The initiative will examine immune, hormonal, and environmental aspects of endometriosis. Endometriosis occurs when tissue similar to that of the endometrium, the uterine lining, is also found in areas outside the uterus, such as on the lining of the abdomen and pelvis, the bowel, bladder and ovaries. The presence of this tissue can cause internal bleeding, scar tissue formation, and inflammation, and can result in pelvic pain, painful menstruation, infertility, and abnormal vaginal bleeding.

According to the results of an Endometriosis Association survey of 4,000 of its members, endometriosis sufferers appear to have an increased risk of breast cancer, melanoma, and ovarian cancer compared with other women. Their families too, may also have a higher than average risk of these conditions, as well as of non-Hodgkin's lymphoma. But the researchers caution that this data is very preliminary. "It's of value, but you have to look at it as: these are women who are members of the Endometriosis Association who are willing to send in a questionnaire. The data, while it's very important to collect, doesn't necessarily represent an unbiased source," Dr. Kevin Osteen, director of the Women's Reproductive Health Research Center at Vanderbilt University Medical School, told Reuters Health. "This sort of data gives us keys as to what the connections might be between disease processes, but there needs to be more research and certainly broader based epidemiology studies before that data can be confirmed."

The health problems experienced by women with endometriosis and their families have been tentatively linked -- by one study published in 1993 on rhesus monkeys -- to environmental exposure to toxins such as dioxin. With a grant from the Environmental Protection Agency, Osteen's research group has been performing additional research on how dioxin may affect the endometriosis disease process. "We have data that we will be publishing soon that shows how dioxin can affect steroid hormone action in a way that could be connected with the disease process.

There is no precise information about how much exposure one would have to have, or whether one's exposure is actually a part of the disease process," Osteen said. "Nobody wants to be an alarmist, because in modern society you can't avoid being exposed to dioxin. We just want to look at the basic mechanisms that dioxin might utilize within the endocrine/immune system, and use that information to help develop some therapeutic options – if it (dioxin exposure) is found to be a part of the diseases process," he added.


By Penny Stern, MD

NEW YORK, Apr 16 (Reuters Health)

--Several advocacy groups involved in autism issues are calling for an investigation into a purported link between the development of autism and vaccination in early childhood. Citing data from a report released by the California Department of Developmental Services that shows a 273% increase in autism diagnoses in that state over the past 10 years, the National Vaccine Information Center, based in Vienna, Virginia, and three other groups are seeking "independent scientific research into whether increased vaccination in early childhood is a contributing co-factor to the development of autism.

"Autism is a mental disorder, usually diagnosed in early childhood, where the individual is withdrawn, and has difficulty relating to other people. Mental retardation, repetitive behaviors such as rocking, and problems with speech are also common in autism. The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, supplied Reuters Health with its position statement on vaccines and autism. Because autism symptoms may become apparent around the age that the measles-mumps-rubella (MMR) vaccine is administered to young children, "autism cases with an apparent onset within a few weeks after MMR vaccination may simply be an . . . unrelated chance occurrence," according to the CDC.

While acknowledging that concerns exist about a relationship between vaccines and autism, the CDC contends that theories seeking to link autism and vaccines are "highly speculative," and that clinical data have not supported such an association. According to the CDC, "To date, there is no convincing evidence that any vaccine can cause autism or any kind of behavioral disorder."

Last year, a group of British researchers announced that they had identified a gastrointestinal-autism syndrome linked to measles-mumps-rubella vaccination. A Finnish group rebutted those findings, reporting that after more than a decade of monitoring, no data were found to support such an association. "No scientific analyses were reported . . . to substantiate the British theory," the CDC comments in its statement.


(April 16) WASHINGTON (Reuters)

-- Cat's claw, a plant extract sold to boost the immune system and reduce inflammation, may work against Alzheimer's disease, researchers said Friday. They said experiments in rats showed the herbal supplement, which comes from a plant found in the Amazon, prevented some of the damage associated with Alzheimer's. Specifically it prevented the deposit of beta-amyloid plaques in the rats' brain, said Alan Snow, a pathology professor at the University of Washington in Seattle.

Alzheimer's, in which the brain slowly deteriorates, is the single most common cause of dementia. It affects four million Americans alone, including former President Ronald Reagan. The Alzheimer's Association predicts that 14 million Americans could be afflicted by the year 2050. There is no known cure although some drugs may slow its progression for a short time.

In Alzheimer's, a protein known as beta-amyloid becomes deformed and is found in unusual deposits, known as plaques, and stringy tangles of brain cells seen in the brains of Alzheimer's patients. But exactly what it does is unclear. Another protein, known as tau, is also involved, but again its role is unclear. Snow and colleagues at the company he helped found, ProteoTech Inc., developed a cat's claw compound they named PTI-00703. Tests in rats and in test tubes indicate it interferes with the formation of these plaques, they told a meeting of the Federation of American Societies for Experimental Biology (FASEB) in Washington, which starts Saturday.

They also mixed the extract with some others, including Ginkgo biloba -- which has been shown in clinical trials to delay some of the symptoms of Alzheimer's in some people -- rosemary and gotu kola. The mixture worked even better, at least in test tubes, than cat's claw alone, they said. ProteoTech said it and Boca Raton-based Rexall Sundown were hoping to start human trials of the cat's claw extract in patients with mild to moderate Alzheimer's.


The American Society for Nutritional Sciences Apr 10, 1999

-- While we hear a great deal about the importance of milk and other calcium-containing foods for bone health, a new study published in the American Journal of Clinical Nutrition shows that fruits and vegetables are also important in the prevention of osteoporosis! The authors evaluated participants from the Framington Heart Study and found that lifelong dietary intakes of potassium, magnesium and fruit and vegetables were determinants of bone mineral density in elderly men and women.

Katherine L. Tucker, PhD, Associate Professor of Nutrition at Tufts University and lead investigator of the study says, "This suggests that a good quality diet in adulthood is important to bone health beyond the better known contributions of calcium and vitamin D, and provides yet another reason to emphasize the intake of fruits and vegetables." According to Dr. Douglas Kiel, Assistant Professor of Medicine at Harvard Medical School and Associate Director of Medical Research at Hebrew Rehabilitation Center for Aged, "Normal digestion produces increased acidity. In this environment, bone acts as a buffer base. Minerals are drawn out of the bone to neutralize the acid, thereby reducing the strength of the bone.

Fruits and vegetables help to prevent this loss of bone mineral density because they create a more alkaline environment in the bodyóthey neutralize the acid without depending on the buffering effects of the bone minerals. It is also possible that potassium and magnesium have direct effects on bone cells." People who consume a lot of highly processed foods often lack adequate amounts of potassium and magnesium. Good sources of potassium include fruits and vegetables such as bananas, oranges, tomatoes, potatoes, broccoli and melon. Good sources of magnesium include a variety of whole foods including fruits and vegetables, milk, fish and whole grains.

Osteoporosis affects roughly 25 million Americans, often leading to bone fractures. Bone is living tissue and its density is constantly affected by diet and exercise. Although the body builds and stores bone more efficiently during the younger years, it is never too late to start healthy bone-building habits. Eating fruits and vegetables can help! This media release by The American Society for Nutritional Sciences and The American Society for Clinical Nutrition is intended to provide information on health and nutrition related research and should not be construed as medical advice. If you have a medical concern, consult your doctor. Source: American Journal of Clinical Nutrition.

Compounds From Fruits, Vegetables And Grains Slow The Growth Of Human Tumor Cells

"I don't think that it's the presence of meat in diets that leads to health problems, but the lack of enough fruits, grains and vegetables. The people who eat a lot of animal products are often the same individuals that don't eat enough fruits and vegetables"

-- Researchers at the University of Wisconsin-Madison report in the current issue of the Journal of Nutrition that small concentrations of two compounds from plants we eat suppress the growth of three kinds of human cancer cells in the laboratory. "Our studies showed that cancer cells were more sensitive to these compounds than normal cells and that the two compounds had a stronger effect when combined than we would have expected from the action of either alone," says Charles Elson, a nutritional scientist in the College of Agricultural and Life Sciences.

"Our findings strengthen the idea that a diet rich in plants is beneficial because of the large array of plant compounds rather than the singular action of one kind of plant or one compound in plants." Elson suggests that the anticarcinogenic activity of these and similar plant compounds differs from the mechanism of other agents that block or suppress cancer cell growth. Unless controlled, cancer cells typically live and divide indefinitely.

"The two compounds we studied suppress an enzyme," Elson says. "We think that this deprives tumor cells of chemical intermediates they need to multiply. The two compounds even work on human tumor cell lines that have mutations known to promote cancer." Studies consistently have shown that people who eat a diet high in fruits, vegetables and grains have a reduced risk of many types of cancer, including lung, alimentary tract, liver, pancreas, bladder, kidney, breast, endometrium, cervix and prostate.

What is it about these foods that limits cancer? In a quest reminiscent of the search for vitamins begun in the last century, scientists are trying to identify the beneficial compounds in the fruits, vegetables and grains we eat that control tumor growth. Plants contain many beneficial compounds including fiber and micronutrients such as vitamins and their precursors. According to Elson, research initially focused on compounds such as vitamin A, vitamin E and folic acid. But clinical trials with them have been inconclusive at best, he says.

Other scientists have been examining non-nutritive compounds in plants. Elson has been studying compounds he calls isoprenoids, a group that includes more than 22,000 compounds. All are derived from a parent compound called mevalonic acid. Limonene and lycopene are examples of isoprenoids that inhibit cancer. Many isoprenoids contribute to plants' distinctive flavors and fragrances, Elson says. In plants, isoprenoids help regulate germination, growth, flowering, and dormancy while attracting pollinators and protecting plants from insects and fungi.

Elson began working with isoprenoids because some can reduce cholesterol levels in animals. Initially he hoped that depriving tumor cells of cholesterol would make them susceptible to cancer treatments. But Elson's early experiments showed he could not lower the cholesterol in tumor cells by feeding animals isoprenoids. However, he noticed that the isoprenoids slowed tumor growth. To screen isoprenoids for those with anticarcinogenic activity, Elson tests them against a cell line developed from an extremely aggressive form of mouse melanoma. He has identified many isoprenoids that can slow the growth of this cell line. The tricky part has been finding isoprenoids that suppress cancer growth at the low concentrations that might occur in diets. One such isoprenoid is gamma-tocotrienol, a compound found in cereal grains; it has a chemical structure related to vitamin E.

In research published in 1997, Elson's group showed that substituting gamma-tocotrienol for vitamin E in a diet fed to mice slowed the growth of tumors transplanted to those mice. It was the first research demonstrating that an isoprenoid slowed cancer growth and prolonged the life of mice when fed at a level that an animal might consume. In the current paper, Elson and his graduate student, Huanbiao Mo, found that gamma-tocotrienol slowed the growth of cell lines from human leukemia and breast cancer.

They also tested beta-ionone -- an isoprenoid found widely in fruits and vegetables. Beta-ionone is related structurally to beta carotene, the precursor of vitamin A. Elson and Mo showed that beta-ionone also suppressed the growth of cell lines for human leukemia and breast cancer, as well as human colon cancer. The human cell lines were even more sensitive to the action of the isoprenoids than the mouse melanoma cells, according to Elson.

"We found that the human cancer cell lines were three times more sensitive to the isoprenoids than a non-cancerous cell line," Elson says. "This raises the issue of why cancer cells might be more sensitive to these plant compounds than non-cancerous cells." Mo and Elson found that the isoprenoids interfered with the maturation of lamin B, a material cells need when they divide. Many of the tumor cells treated with the isoprenoids accumulated in a pre-division phase while many others entered apoptosis, or programmed cell death. The researchers showed that the isoprenoids suppressed the activity of 3 hydroxy-3-methyglutaryl coenzyme A (HMG CoA) reductase, an enzyme critical for the maturation of lamin B as well as the synthesis of cholesterol. "We've known since the 1950s that tumor cells are more sensitive to reductions of HMG CoA reductase than healthy cells," Elson says. "When isoprenoids inhibit the activity of this enzyme they disrupt the processing of mevalonic acid via the mevalonate pathway. We think the tumor cells need chemical intermediates produced from the breakdown of mevalonic acid for lamin B maturation and that isoprenoids slow tumor growth by depriving tumor cells of those intermediates."

The nutritional scientist does not anticipate that his research will lead to a single critical isoprenoid or vegetable that people can eat to protect themselves from cancer. "These compounds act as a group to inhibit cancer growth," he says, "with some enhancing the effectiveness of others." Nor does Elson believe in an exclusively vegetarian diet. "I don't think that it's the presence of meat in diets that leads to health problems, but the lack of enough fruits, grains and vegetables. The people who eat a lot of animal products are often the same individuals that don't eat enough fruits and vegetables," he says. Writer: George Gallepp, 608-262-3636


First study to show that men's muscle strength is a powerful predictor of physical disability.

-- Hand grip strength in midlife can be used for early screening of people at increased risk of physical disability in old age, according to an article in the February 10 issue of The Journal of the American Medical Association (JAMA).

Taina Rantanen, Ph.D., formerly of the National Institutes of Health, Bethesda, Md., Jack M. Guralnik, M.D., Ph.D., and colleagues conducted a study to determine whether hand grip strength measured during midlife predicts old age functional limitations and disability in initially health men. The study was a 25-year prospective cohort study that began in 1965 among Japanese-American men living on Oahu, Hawaii. The study included 6,089 men who were healthy at baseline. Taina Rantanen, Ph.D., is now with the University of Jyvaskyla, Finland.

"Among healthy 45- to 68-year-old men, hand grip strength was highly predictive of functional limitations and disability 25 years later," write the authors. "Good muscle strength in midlife may protect people from old age disability by providing a greater safety margin above the threshold of disability."

The researchers found that the risk of self-care disability was more than two times greater in the lowest vs. the highest grip strength group. They add that hand grip strength has been found to correlate with strength of other muscle groups and is thus a good indicator of overall strength. Consequently, grip strength measurements could be used for screening to identify those at higher risk of physical disability related to low muscle strength. Muscle strength was found to track over the life span: those who had higher grip strength during midlife remained stronger than others in old age.

According to the authors, explanations for their results include the possibility that people with greater muscle strength during midlife may be at a lower risk of becoming disabled because of their greater reserve of strength regardless of chronic conditions that may develop. In addition, they believe that the reserve capacity may serve as a safety margin that helps prevent functional limitations from developing (e.g., following inactivity and deconditioning associated with surgery or an acute illness).

The researchers write that for people with low muscle strength, exercise interventions aimed at improving strength in all muscle groups could potentially lower the risk of subsequent physical disability. Muscle strength can be increased substantially by physical exercise at all ages. (JAMA. 1999; 281:558-560)

ww The National Cancer Institute wants to bring new information regarding the optimal duration of adjuvant tamoxifen therapy to the attention of clinicians. Recent results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-14, that evaluated 5 years versus 10 years of adjuvant tamoxifen for early stage breast cancer, indicate no advantage for continuation of tamoxifen beyond 5 years in women with node-negative, estrogen receptor-positive breast cancers.

In view of the proven benefits of 5 years of adjuvant tamoxifen, this treatment should continue to be administered whenever appropriate to women with early stage breast cancer. However, the new data suggest that more than 5 years of adjuvant treatment is not warranted in routine clinical practice in this patient population.

Increasing Prevalence of Antimicrobial Resistance Among Uropathogens Causing Acute Uncomplicated Cystitis in Women

-- Kalpana Gupta, MD, MPH Delia Scholes, PhD Walter E. Stamm, MD Context Guidelines for the management of acute uncomplicated cystitis in women that recommend empirical therapy (!) (HC) in properly selected patients rely on the predictability of the agents causing cystitis and knowledge of their antimicrobial susceptibility patterns.
ad Objective: To assess the prevalence of and trends in antimicrobial resistance among uropathogens causing well-defined episodes of acute uncomplicated cystitis in a large population of women.

Design: Cross-sectional survey of antimicrobial susceptibilities of urine isolates collected during a 5-year period (January, May, and September 1992-1996). Setting Health maintenance organization. Patients: Women aged 18 to 50 years with an outpatient diagnosis of acute cystitis. Main Outcome Measures Proportion of uropathogens demonstrating in vitro resistance to selected antimicrobials; trends in resistance over the 5-year study period. Results Escherichia coli and Staphylococcus saprophyticus were the most common uropathogens, accounting for 90% of the 4342 urine isolates studied. The prevalence of resistance among E coli and all isolates combined was more than 20% for ampicillin, cephalothin, and sulfamethoxazole in each year studied. The prevalence of resistance to trimethoprim and trimethoprim-sulfamethoxazole rose from more than 9% in 1992 to more than 18% in 1996 among E coli, and from 8% to 16% among all isolates combined.

There was a statistically significant increasing linear trend in the prevalence of resistance from 1992 to 1996 among E coli and all isolates combined to ampicillin (P<.002), and to cephalothin, trimethoprim, and trimethoprim-sulfamethoxazole (P<.001). In contrast, the prevalence of resistance to nitrofurantoin, gentamicin, and ciprofloxacin hydrochloride was 0% to 2% among E coli and less than 10% among all isolates combined, and did not change significantly during the 5-year period.

Conclusions: While the prevalence of resistance to trimethoprim-sulfamethoxazole, ampicillin, and cephalothin increased significantly among uropathogens causing acute cystitis, resistance to nitrofurantoin and ciprofloxacin remained infrequent. These in vitro susceptibility patterns should be considered along with other factors, such as efficacy, cost, and cost-effectiveness in selecting empirical therapy for acute uncomplicated cystitis in women. JAMA. 1999;281:736-738

PARIS, Feb. 12 The attorney general of France announced a court decision to impose a seven year prison sentence on a Malian woman who is accused of mutilating the genitals of 48 young girls. (see Circumcision)


New Muscle Disease Identified In France

-- A new muscle disease called macrophagic myofasciitis is being seen with increasing frequency in France. As reported in the journal The Lancet (August 1, 1998) by Gherardi and colleagues, the first case was identified in 1993. Seventeen additional cases have been evaluated through 1997 in several French centers for the study and treatment of muscle disorders.

Macrophagic myofasciitis is named for the findings seen in tissue from muscle biopsies. Microscopic examination has shown an abnormal infiltrate of specialized immune cells called macrophages surrounding muscle tissue. Macrophages are a type of immune cell that is important for swallowing and destroying microorganisms. They also assist other immune cells in the body’s response to invading organisms. The muscle cells involved in patients with this disease appear to be minimally damaged by the macrophages. Muscle pain is the most frequent symptom. This can be localized to the limbs or be more diffuse. Other symptoms include joint pain, muscle weakness, fatigue, fever, and muscle tenderness.

The disorder is associated with an altered immune system in some, but not all, patients. A significant number of patients with macrophagic myofasciitis had taken chloroquine or hydroxychloroquine for malaria; these drugs are known to inhibit the secretion from macrophages of a cell messenger molecule called interleukin. The cause of macrophagic myofasciitis has not been identified despite fairly extensive investigations into known infectious and immune disorders which might cause muscle disease. A unique material that accumulates within the affected macrophages has been seen on electron microscopy. This material has yet to be characterized. Most of the patients with macrophagic myofasciitis have responded to treatment with antibiotics and/or steroids within a few days or weeks. One patient with macrophagic myofasciitis and evidence of tuberculosis exposure recovered following treatment of the tuberculosis with four drugs. With macrophagic myofasciitis, a mysterious new disease of muscle has been identified.

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