STUDY: Lifestyle-related diseases

JOURNAL: Department of Epidemiology, Radiation Effects Research Foundation, Hijiyama, Minami-ku, Hiroshima 732-0815, Japan

AUTHORS: Kei Nakachi

ABSTRACT: Lifestyle-related diseases, including cancer and cardiovascular disease, are also characterized as aging-related diseases, where aging may be the most potent causal factor.

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COMMENTARY: In light of this, prevention of lifestyle-related diseases will depend on slowing the aging process and avoiding the clinical appearance of the diseases. Green tea is now accepted as a cancer preventive on the basis of numerous in vitro, in vivo and epidemiological studies.

In addition, green tea has also been reported to reduce the risk of cardiovascular disease. We found an apparent delay of cancer onset/death and all cause deaths associated with increased consumption of green tea, specifically in ages before 79 in a prospective cohort study of a Japanese population with 13-year follow-up data.

This is consistent with analyses of age-specific cancer death rate and cumulative survival, indicating a significant slowing of the increase in cancer death and all cause death with aging.

These results indicate that daily consumption of green tea in sufficient amounts will help to prolong life by avoiding pre-mature death, particularly death caused by cancer.

STUDY: Environmental Risks for Cancer in Kids

JOURNAL: Environmental Protection Agency

AUTHORS: Ramona Trovato

ABSTRACT: Children under 2 years of age have a much greater chance of getting cancer from exposure to certain chemicals than do adults, the Environmental Protection Agency concludes in a new risk assessment.

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COMMENTARY: According to the analysis, which focused chemicals that cause damage to genes, the risk of a future cancer is 10 times greater for a child under age 2 than for an adult who is similarly exposed.

Children from 3 to 15 years of age face a risk at least three times greater than adults when exposed to these chemicals, the proposed EPA guidance said.

The analysis was confined to so-called mutagenic chemicals that cause damage to genes thereby making a person more susceptible to getting cancer later in life.

But EPA scientists said children may well be more vulnerable when exposed to other types of cancer-causing chemicals as well, although the scientific data is not yet sufficient to make any conclusions on that.

Nevertheless, the proposed guidance would represents a major change in how cancer risk to children is viewed by EPA regulators. Currently the agency assumes in when assessing a chemical that children are no more vulnerable to cancer than adults if exposed to the substance.

"This (new assessment) is really a significant step forward in understanding how environmental exposure affects our children," said Ramona Trovato, an EPA official who has spent the last five years studying environmental pollution and children.

The proposed guidelines on children is to be reviewed by the EPA science advisory board, probably in May, with a final guidance likely to be issued this summer, said Bill Farland, the EPA's acting assistant administrator for science.

"We think this guidance on assessing children's cancer risk is going to evolve for a number of classes of compounds ... as we get more information. "We have long talked about the need to assure that we're protecting sensitive sub-populations and sensitive life stages."

The EPA assessment notes that children generally are expected to have exposures to chemicals that are different from adults because differences in their size, physiology and behavior. Children and adults exposed to the same concentrations of a chemical also may receive different internal doses because of differences in intake and absorption rates, the assessment said.

The EPA assessment was based mainly on a review of animal studies involving five mutagenic compounds and from data collected in studies of survivors of atomic bomb blasts in Japan at the end of World War II, said James Cogliano, an EPA scientist.

Most of the chemicals that were studied involve industrial applications, ones to which infants would not likely be easily exposed, said Farland.

One of them, benzopyrene, is a carcinogen found in cigarette smoke and auto exhausts; another, benzidine is used in the manufacture of dyes, while a third, vinyl chloride, is used in making plastics.

But the findings suggest, when more studies come in, the same disparity on risk between adults and the very young may well be observed although in existing studies "you see mixed results," said Cogliano. "Sometimes there was a higher cancer risk, sometimes there was not."

Environmentalists embraced the new focus on children.

"We're very happy that they've recognized that children under 2 years of age are really very susceptible," said Jennifer Sass, a scientist in the public health program at the Natural Resources Defense Council.

EPA officials said the new guidelines will more accurately reflect cancer risks than methods now in use.

STUDY: Procedure detects change in structure of blood protein

JOURNAL: Ischemia Technologies

AUTHORS: FDA

ABSTRACT: Doctors have won federal approval of a new blood test to help them tell which patients suffering chest pain aren’t really having a heart attack.

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COMMENTARY: The FDA approved a simple blood test that, when added to heart checks, could greatly improve doctors’ ability to rule out a heart attack and send those patients home sooner. The $30 test, made by Ischemia Technologies Inc. of Denver, uses the metal cobalt to hunt changes in a blood protein that occur during a heart attack.

Today, two tests are standard for heart-attack detection: an EKG to measure the heart’s electrical activity, and a blood test that detects troponin, a protein present in the blood after a heart attack.



In a study of 200 patients, doctors were 50 percent accurate in ruling out a heart attack using just an EKG and troponin test. But when they added the new test, doctors accurately ruled out a heart attack 70 percent of the time, FDA said.

A blood protein called albumin undergoes changes in its structure during a heart attack and certain other illnesses. In 1995, a Denver emergency room physician discovered that when cobalt was added to a blood sample, more of the metal would bind to normal albumin than to the changed albumin of a heart-attack victim.

The company created a way to measure that cobalt-albumin reaction using chemical-analyzing equipment standard in hospital laboratories.

But the new test must be used with standard heart-attack tests. It’s far from perfect, so using it alone could prove deadly, FDA’s Gutman said.

STUDY: Increases the activity of brain acetylcholine and choline acetyltransferase

JOURNAL: 28th International Stroke Conference: Abstract P327. Presented Feb. 14, 2003.

AUTHORS: Jinzhou Tian, MD

ABSTRACT: Ginseng may help improve memory in patients with mild dementia following a stroke, according to the results of a randomized pilot study reported at the American Stroke Association's 28th International Stroke Conference.

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COMMENTARY: Chinese ginseng has been used for centuries in China to treat disease and aging.

Chinese ginseng strikingly improves learning and memory following transient cerebral ischemia in rats. It increases the activity of brain acetylcholine and choline acetyltransferase in aged mice, while reducing the activity of acetylcholinesterase in the cerebral cortex and hippocampus.

In this randomized, double-blind, controlled clinical trial, 40 patients with mild and moderate dementia after ischemic stroke (26 men and 14 women) received one tablet of compound Chinese ginseng (n = 25) or one 40-mg tablet of almitrine + raubasine (n = 15), three times daily for 12 weeks.

The ginseng compound was extracted from Chinese ginseng roots, leaves, and panax notoginseng. The combination of almitrine and raubasine is thought to increase oxygenation in brain tissue.

After treatment with Chinese ginseng, mean scores on the HVLT and total memory scores increased significantly (P < .05 and P < .001, respectively).

Improvements in episodic memory function assessing immediate and delayed story recall, delayed word recall, verbal learning and verbal recognition, and visual recognition were greater in the ginseng group than in the almitrine + raubasine group.

"There is currently great interest in studying herbs used in traditional forms of medicines, and the problem of dementia after stroke is a significant one," says Robert J. Adams, MD, chairman of the Stroke Council of the American Heart Association. "This work showing that ginseng may improve memory after stroke needs to be further studied, with larger sample sizes. A placebo-controlled study would also be the next step.

STUDY: Conditions in the womb, which can influence birth size, might also influence the risk of breast cancer later in life.

JOURNAL: BMJ 2003;326:248-251.

AUTHORS: Dr. Valerie McCormack

ABSTRACT: Birth size, as determined by birth length and head circumference, is directly related to the risk of developing premenopausal breast cancer.

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COMMENTARY: However, the link between birth size and breast cancer was not seen among women older than 50 years of age, lead author Dr. Valerie McCormack, from the London School of Hygiene and Tropical Medicine.

Dr. McCormack said that the current study was undertaken to investigate how conditions in the womb, which can influence birth size, might also influence the risk of breast cancer later in life.

Based on the findings, Dr. McCormack suggested that larger infants may have been exposed to different levels of growth hormones in the womb, and that the in utero environment may have played a role in determining breast cancer risk.

In the study, the researchers reviewed information from 5358 singleton females born between 1915 and 1929. Data from the Swedish Cancer Registry were analyzed to determine which subjects developed breast cancer.

The researchers found that 359 of the subjects developed breast cancer, with a median age at diagnosis of 62 years.

Women who weighed at least 4000 g at birth were 3.5 times more likely to develop breast cancer than were women with birth weights below 3000 g.

Although birth weight was related to breast cancer later in life, the link was no longer significant after accounting for birth length and head circumference. In contrast, birth length and head circumference remained significant predictors of future disease even after adjusting for birth weight.

Among infants of similar birth size, the researchers found that the gestational age at birth was inversely related to the risk of breast cancer.

These findings suggest that the hormones that influence body length and head circumference also play an important role in later cancer risk.

STUDY:

JOURNAL: Ann Intern Med 2003;138.

AUTHORS: Dr. Bent

ABSTRACT: Compared with other herbal products, ephedra is far more likely to cause adverse effects.

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COMMENTARY: Based on an analysis of reports to the American Association of Poison Control Centers, Dr. Stephen Bent and his colleagues discovered that products with ephedra accounted for 64% of the herb-related adverse reactions in 2001.

This finding is remarkable, the authors note, given that less than 1% of herbal products sold that year contained ephedra.

Although awareness of the potential dangers of ephedra is growing among consumers, many still purchase ephedra-containing products.

Using data from case reports alone, it has been difficult to definitively link ephedra with various adverse effects, Dr. Bent said. But the finding that ephedra is linked to far more side effects than other herbs adds support to the theory that the substance can be dangerous, he said.

How ephedra stacked up against other products varied from herb to herb, Dr. Bent and his colleagues note -- but in all cases, it outnumbered other products in adverse reactions.

Overall, there were 1178 adverse reactions reported for ephedra, compared with 28 for ginkgo biloba, 31 for St. John's wort and 69 for Echinacea, among others.

My Comment is that Ephedra has always been the whipping boy of the herbal industry. Used properly I have never had a problem with it. It is the abuse of it that causes the issue.

Like everything else I don't see alcohol or tobacco being banned and these two items cause far greater adverse outcomes.

STUDY: . A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen.

JOURNAL: Phytomedicine 2000; 7(2): 85-89.

AUTHORS: Spasov AA, Wikman GK, Mandrikov VB, et al.

ABSTRACT: A placebo-controlled, Russian clinical study showed that an extract of Rhodiola rosea enhanced physical fitness, improved neuro-motor test responses, reduced mental fatigue, and improved general well being in a group of healthy foreign medical students undergoing a stressful exam period.

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COMMENTARY: The 40 study participants, all Indian men between the ages of 17 and 19, were randomly assigned to take either placebo or Rhodiola extract at a dose of 50 mg twice daily.

The most significant differences between groups were seen in physical fitness, mental fatigue, neuro-motor tests, and well being; no significant differences were observed in results of correction tests or tapping speed tests.

No adverse events were reported. As the dose of Rhodiola employed in this study was lower than that used in previous studies, the researchers concluded, "...the study drug gave significant results compared to the placebo group but that the dose level probably was suboptimal."

According to the authors, the majority of earlier studies on the anti-fatigue and performance-enhancing effects of Rhodiola utilized single doses more than three times higher than the dose used in their study.

When used in psychiatric practice for the treatment of asthenic syndromes (weakness and debility), doses 15 times as high are used for periods of one to two months.

STUDY: Women who most often ate a Western diet were 46% more likely to develop colon cancer

JOURNAL: Arch Intern Med 2003;163:309-314.

AUTHORS:

ABSTRACT: Women who routinely consume a diet high in red meats, fats, and refined grains are at increased risk for colon cancer.

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COMMENTARY: Although the notion that consumption of a "Western diet" may promote colon cancer is not novel, several reports have failed to establish an association, the authors point out.

For example, in a study of more than 60,000 women reported last year, consumption of a Western diet was not tied to an increased risk of colorectal cancer.

In the current study, women who most often ate a Western diet were 46% more likely to develop colon cancer than their peers who rarely consumed such a diet. In contrast, consumption of a Western diet was not tied to an increased risk of rectal cancer.

The findings are based on a study of 76,402 women who participated in the Nurses' Health Study and were questioned about their dietary habits in 1984, 1986, 1990, and 1994. The women ranged in age from 38 to 63 years and none had a history of cancer in 1984.

The women were classified according to how well their diet matched a Western diet pattern as well as a "prudent" pattern, defined as a diet high in fruits, vegetables, fish, poultry, and whole grains.

During the 12-year follow-up period, 445 cases of colon cancer and 101 cases of rectal cancer were observed, the authors note.

Compared with low adherence to a prudent diet, strict adherence to this dietary pattern was associated with a 29% reduction in the risk of colon cancer. Still, this association failed to reach statistical significance.

"We found that a diet high in red and processed meats, refined grains, and other characteristics of the Western pattern was associated with a higher risk of colon cancer in women," the researchers state. "Our study provides further evidence that switching from a typical Western diet to a more prudent diet may reduce that risk of colon cancer," they add.

STUDY: Take your Probiotics

JOURNAL: Am J Clin Nutr. 2003;77:517-520

AUTHORS: Ulrich Gluck

ABSTRACT: A probiotic drink reduces nasal carriage of potentially pathogenic bacteria (PP better than yogurt does.

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COMMENTARY: "As a bacterial reservoir, the nose may harbor PPB: Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococci, and Haemophilus influenzae," write Ulrich Gluck, from the Swiss National Accident Insurance Institute in Lucerne, Switzerland, and colleagues.

"In patients carrying PPB, antiseptic regimens could be crucial for infection control after major operations on or injuries of the head, nasal sinuses, or lungs. Such regimens may also be important for diabetic patients and persons receiving hemodialysis, in intensive care units, or with impaired immunity due to various other causes."

For three weeks, 209 volunteers consumed either 65 mL of a probiotic, fermented milk drink or 180 g of standard yogurt once daily. The probiotic contained Lactobacillus GG (ATCC 53103), Bifidobacterium sp B420, Lactobacillus acidophilus 145, and Streptococcus thermophilus. Microbial examination on days 1, 21, and 28 was blinded to the source of the samples.

In the group that consumed the probiotic drink, nasal PPB decreased by 19% from baseline (P < .001), primarily because of a decrease in gram-positive bacteria (P < .05). The group that consumed yogurt had no significant reduction in nasal PPB.

"An orally administered fermented milk product containing the probiotic bacterium Lactobacillus GG significantly reduces the occurrence of nasal colonization with PPB," the authors write.

"The mechanisms underlying this result may have involved stimulation of the B lymphocytes of the gut-associated lymphoid tissue, which may have migrated to the upper respiratory immune system."

The investigators suggest that the migrating GALT B lymphocytes (which produce serum immunoglobulin A subclass 2 rather than subclass 1) usually produced in nasal and bronchial lymphoid tissue, may help eliminate the PPB, which often produce SIgA1-specific proteases. They plan to test this hypothesis by measuring the concentrations of both SIgA1 and SIgA2 in nasal lavage samples before and after probiotic ingestion.

STUDY: Latest research suggests DNA even more to blame for weight

JOURNAL: Howard Hughes Medical Institute at The Rockefeller University in New York City

AUTHORS: Dr. Jeffrey Friedman

ABSTRACT: Despite all the public service announcements telling people how unhealthy it is to be fat, Americans just keep larding on the pounds. Studies have shown that as many as 60 percent of the U.S. population is overweight, while almost 30 percent is classified as obese. Some say the fast-food industry is to blame while others fault super-sized meal portions. But is it just a problem of unhealthy lifestyles or is there something else going on deep down in our cells?

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COMMENTARY: Why the sudden change in weight-loss philosophy? It’s simple. Scientists have learned that while willpower is important, much of what, when and how much we eat is dependent on our genes. In addition, the urge to exercise may also be related to the DNA we inherit.

When it comes to losing weight, we’re fighting against a body regulatory system that has evolved over hundreds of thousands of years to keep us functioning no matter how sparse food becomes. And, scientists have been learning, this genetic influence is stronger in some people than others.

As a prime example of the role of genetics, researchers point to two groups of Pima Indians, one living in Arizona and the other in Mexico’s Sierra Madre Mountains. The Pimas in Arizona have long been known for high rates of obesity, diabetes (almost 50 percent suffer from this disease) and high cholesterol.

The Pimas in Mexico, where food is more sparse and manual labor more common, tend to be lean and have a much lower rate of diabetes than those in Arizona. But despite their healthier lifestyles, the Mexican Pimas still have higher rates of obesity and diabetes than the general population, a finding that leads researchers to point to genes as the culprit.

After studying groups like the Pimas, scientists have developed a theory known as “The Thrifty Gene Hypothesis.” This idea suggests that some of us are born with the Honda of metabolisms — we can go a long way with little fuel.

Other, more fortunate people — fortunate, that is, in times of plenty — have metabolisms that more closely resemble gas-guzzling SUVs. They burn fuel fast leaving bodies slim.

In 1994, when researchers discovered the chemical compound leptin, they thought they had come up with a cure for people with thrifty genes. Leptin is released by fat cells and the larger fat cells get, the more leptin they release.

Normally, when the brain gets a surge of leptin, it concludes that the body has a safe store of fat and sends out a message to dampen appetite.

But, much to their dismay, when scientists tried giving overweight people more leptin to see if it would kill appetite and cause weight loss, the experiments failed.

Most obese people already have high levels of leptin,” explains Dr. Jeffrey Friedman, an investigator with the Howard Hughes Medical Institute at The Rockefeller University in New York City. “But they seem to be insensitive to it.”

Friedman suspected that there might be a way to bypass leptin by looking at enzymes the hormone regulates. Last summer, he and his colleagues found an enzyme related to weight control called SCD-1 and studied the effects of the enzyme in mice genetically engineered to be deficient in it. These mice tended to stay thin, even though they ate more than normal mice, because they had faster metabolisms.

Apparently, the body needs SCD-1 in order to store fat and, without the enzyme, most fat is burned instead of being stashed away.

Another factor in determining whether someone will be heavy or not is the amount time they spend working out. But new research suggests that whether one chooses to become a couch potato may also be the result of their DNA.

Researchers looking at a gene labeled Nh1h2 found that mutations of the gene impacted the impulse to exercise. Mice with certain mutations of Nh1h2 tended to be lethargic.

“Basically, if you put a normal mouse in a cage with an exercise wheel, he’ll run,” explains Deborah Good, an assistant professor of vertebrate molecular genetics at the University of Massachusetts in Amherst.

“But the mutant ones, if you put them in a cage with a wheel, they’re not interested in running,” says Good. “There’s nothing physically wrong with them. They did as well or better in tests with forced exercise. They just don’t want to run.”

While genes may ultimately explain why some of us tend to be pudgy and others stay slim, research into one’s DNA won’t offer any practical help with weight loss for the time being, experts say.

“At present, we’re at least five years away from having any therapeutic applications based on genes,” says Thomas Wadden, director of the Weight and Eating Disorders Program.

STUDY: Young women need new treatment programs

JOURNAL: National Center on Addiction and Substance Abuse at Columbia University

AUTHORS: Joseph A. Califano Jr

ABSTRACT: Young girls and women are more easily addicted to drugs and alcohol, have different reasons than boys for abusing substances and may need single-sex treatment programs to beat back their addictions.

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COMMENTARY: "They get hooked faster, they get hooked using lesser amounts of alcohol and drugs and cocaine, and they suffer the consequences faster and more severely,” said Joseph A. Califano Jr., chairman of the National Center on Addiction and Substance Abuse at Columbia University, which conducted the survey of girls and young women over three years.

“With some exceptions the substance abuse prevention programs have really been designed with a unisex, one-size-fits-both-sexes mentality,” Califano said. “We now know that girls are different than boys - let’s recognize it and let’s help them.”

The study, based on a nationwide survey of females age 8 to 22, found the gender gap is narrowing between boys and girls who smoke, drink and use drugs.

Approximately 45 percent of high school girls drink alcohol, compared with 49 percent of boys, and girls outpace boys in the use of prescription drugs, the study found.

While boys often experiment with cigarettes, alcohol and drugs in a search for thrills or heightened social status, girls are motivated by a desire to reduce stress or alleviate depression, the study found.

Girls are also more likely to abuse substances if they reached puberty early, had eating disorders or were ever physically or sexually abused, researchers said.

Their likelihood of using cigarettes, alcohol or drugs also increases when they move to a new community, or advance from middle school to high school or from high school to college.

Califano said more treatment centers need to give female recovering addicts “a chance to be with just women,” adding that substance abusers who were victims of physical abuse may not respond well to a group with men.

Some traditional confrontational methods of beating addiction may also be the wrong approach for women, researchers found.

Califano said facilities like the Betty Ford Center, which now has separate treatment programs for men and women, may be the model for future success.

“We have not put together prevention programs that go to the things that influence girls and influence young women,” Califano said. “Women have paid a fearful price for this failure.”

The study recommends that parents, educators and doctors do more preventive work with girls who fall into the various risk categories.

It also faults alcohol and tobacco companies for promoting their products by linking them to glamorous models, and calls for a ban on alcohol advertising on television and cigarette and alcohol advertising in magazines with large numbers of young readers.

STUDY: You are what you ate, breathed, drank and more

JOURNAL: CDC

AUTHORS: Dr. David Fleming

ABSTRACT: Researchers say toxic chemicals make their way into our bodies every day through a range of products from cosmetics and food additives to pesticides and building materials.

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Two recent studies cast dramatic light on the extent to which Americans are absorbing toxic chemicals in their bodies as part of everyday life. They present a striking picture of Americans riddled with low levels of chemicals, the vestiges of eating, drinking, breathing and touching the synthetic products of the industrial world. Given how common these chemicals are, can personal actions and better choices reduce one’s level of exposure in a toxic world?

COMMENTARY: C Brody used to think so. For 20 years, she ate organic produce and followed all the usual recommendations to reduce chemical exposure, from using non-toxic household cleaning detergents to avoiding pesticides in her home and garden.

Joking that she washed her bathtub in vinegar so much that her family said it smelled like a salad, she adds, “I’m the one hand-picking individual weeds from my garden rather than using chemical sprays, and going that extra mile to get my organic milk in a glass bottle.”

With more than 70,000 chemicals in use in the United States and 2,000 new compounds being introduced every year, according to government figures, the average American is exposed to a cocktail of chemicals from various sources.

Brody used to think her efforts helped limit her exposure, but after volunteering to take part in a study measuring toxic chemicals in her body, she was shocked to find that she still had some 85 toxic chemicals in her blood and urine.

“I’m proof that a healthy lifestyle doesn’t shield you,” says Brody.

Brody and eight other volunteers were tested for the presence of 210 chemicals, commonly found in consumer products and industrial pollutants, by the Mt. Sinai School of Medicine in New York and two non profit groups, the Environmental Working Group and Commonweal.

The study claims to be “the most comprehensive” survey to date of the multitude of contaminants found in humans.

Tests on blood and urine detected an average of 91 industrial compounds, pollutants and other chemicals in the volunteers, with a total of 167 chemicals found across the entire group. The researchers chose subjects who did not work with chemicals in their jobs or live in industrial areas.

This small Mt. Sinai study and a much more comprehensive survey done by the Centers for Disease Control, also released in January, shed new understanding on the “body burden” of toxic chemicals we all carry inside. The results illustrate a side effect of modern life in which everything from carpets to cosmetics are bathed in toxins.

The CDC tests measured some 116 harmful chemicals, including lead, mercury and other heavy metals, chlorinated solvents, insecticides and other pesticides, PCBs, and plasticizing agents called phthalates, to name but a few.

The agency noted some public health successes, such as a decline in lead levels and in cotinine, the byproduct of tobacco smoke. But the researchers also announced some troubling findings, including:

Children have twice the levels of certain pesticides in their blood as adults Children have higher levels of cotinine than adults

Children have higher levels of certain chemicals used in soft plastic toys Adolescents have high levels of phthalates from personal care products

Mexican-Americans have three times the levels of the banned pesticide DDT in their systems as other Americans.

Rather than be paralyzed by our toxic exposure, we ought to use the results of these studies to promote better policies and product lines.

STUDY:

JOURNAL: Cancer Cytopathol 2002;96:338-343.

AUTHORS: Dr. Raheela Ashfaq

ABSTRACT: The ThinPrep Pap test (Cytyc, Boxborough, Massachusetts) is more sensitive in detecting cervical and endometrial adenocarcinomas than is the conventional Pap smear.

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COMMENTARY: Dr. Raheela Ashfaq and colleagues from the University of Texas Southwestern Medical Center, Dallas, evaluated women with atypical glandular cells of undetermined significance (AGCUS) or adenocarcinomas diagnosed between 1998 and 2000 using the ThinPrep method. The control group included women who underwent conventional smears obtained between 1996 to 1998. Histological follow-up was performed for all patients.

Of 112,058 ThinPrep Pap tests, 186 (0.17%) were found to be AGCUS/adenocarcinomas, the researchers report. Of the 83,464 conventional smears, 77 (0.09%) were interpreted as AGCUS/adenocarcinomas.

The overall sensitivity in detecting cervical and endometrial adenocarcinomas was higher with the ThinPrep Pap test (72%) than with the conventional Pap smear (41.5%, p < 0.001).

"We believe that the introduction of the ThinPrep Pap test in our laboratory has resulted in a significant improvement in the detection of glandular lesions," the investigators conclude. "Our findings suggest that this system can facilitate a more directed approach to the evaluation and treatment of cervical and endometrial adenocarcinomas."

STUDY: people should strongly consider taking additional folic acid

JOURNAL: BMJ 2002;325:1202-1206.

AUTHORS: Dr. Wald

ABSTRACT: Increasing folic acid intake to lower concentrations of homocysteine would significantly reduce the risk for ischemic heart disease, deep vein thrombosis and stroke.

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COMMENTARY: For quite some time an association between homocysteine and cardiovascular disease has been recognized, but there has been considerable doubt as to whether this association is causal.

To investigate the causal role of homocysteine in cardiovascular disease, Dr. Wald from Southampton General Hospital, UK, and colleagues performed a meta-analysis of 72 studies in which the prevalence of a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was determined in 16,849 cases and controls.

They also analyzed 20 prospective studies, which included 3820 subjects and measured the relationship between homocysteine and disease risk.

Dr. Wald's team found a significant association between homocysteine and the risk for ischemic heart disease, deep vein thrombosis and stroke. A 5-mol/L increase in homocysteine was associated with an increased risk of ischemic heart disease in both the genetic studies (odds ratio 1.42) and in the prospective studies (odds ratio 1.32).

The same association was seen for deep vein thrombosis with and without pulmonary embolism (odds ratio in genetic studies 1.60; there were no prospective studies), and for stroke (odds ratio 1.65 in the genetic studies and 1.59 in the prospective studies), the researchers report.

Dr. Wald and colleagues conclude that "our results strengthen the evidence that a raised serum homocysteine concentration is a cause of cardiovascular disease."

They base their conclusions on their analysis of both genetic and prospective studies, which while susceptible to different types of error both found similar associations between homocysteine and cardiovascular disease.

They also note that homocystinurias cause high homocysteine levels and a high risk of premature cardiovascular disease, and that "lowering serum homocysteine reduced risk in both a randomized trial in patients with heart disease and in patients with homocystinuria."

They add that "on this basis, lowering homocysteine concentrations by 3 mol/L from current levels (achievable by increasing folic acid intake) would reduce the risk of ischemic heart disease by [an average of] 16%, deep vein thrombosis by 25% and stroke by 24%."

Dr. Wald advises that "people should strongly consider taking additional folic acid to lower their risk of cardiovascular disease." The priority groups are those with existing cardiovascular disease, but all those over 55 years of age should consider taking folic acid to reduce their risk, he added.