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New Technique Shows Drug Effects in the Human Brain

Researchers at the Brain Imaging Center of McLean Hospital in Belmont, Massachusetts, have published the first research study showing the cocaine-induced changes in the blood vessels within the human brain.

Cocaine-induced strokes are rare but increasing, and are presumed to be caused by a drug-induced spasm in the vessels nourishing the brain. Many researchers have studied drug effects by administering drugs to animals and then dissecting the animals’ brains.

The McLean team used a technique called magnetic resonance angiography to study the brain blood vessels in 24 healthy men in their 20s and 30s who reported a history of occasional cocaine use. The researchers administered a single low dose of cocaine intravenously and observed brain function 20 minutes later.

The researchers found that, indeed, even low-dose cocaine constricts brain blood vessels, sometimes severely, supporting concerns that it can cause either acute or gradual loss of brain cells.

Kaufman MJ, Levin JM, Ross MH, et al. Cocaine-induced cerebral vasoconstriction detected in humans with magnetic resonance angiography. JAMA. 1998;279:376-380.

Yet Another Saccharin Report: Rat Tests Don’t Apply

Saccharin packets carry warnings about possible cancer risk based on rat experiments. But after three decades, tests of saccharin on animals have clearly shown only one thing: the tests can’t be trusted.

The Journal of the National Cancer Institute of January 7, 1998, reported results of long-term saccharin tests on monkeys and used the opportunity to raise fundamental questions about the value of animal safety tests.

Mice do not get cancer from eating saccharin. Neither do hamsters, guinea pigs, or, for that matter, monkeys, according to the latest series of tedious long-term tests. Monkeys fed saccharin in baby bottles as infants and mixed with bread as adults in tests lasting from 6 to 25 years showed no cancer risk. An accompanying editorial, however, criticized the study’s choice of dosages, species, and numbers, and reminded readers of the need for reducing, refining, and replacing animal tests.

None of these tests has been able to trump human epidemiologic studies, which show none of the effects seen in rats.

Male rats fed saccharin apparently develop bladder cancers because of a chain of events that does not occur in humans. When rats ingest large amounts of any sodium salt—sodium saccharin, sodium ascorbate, or others—a calcium phosphate-containing precipitate forms in their urine. This only happens when there is a pH over 6.5 and a large concentration of protein, calcium, and phosphate in the urine. Rats have 100 to 1,000 times greater protein concentration in their urine, compared to humans, and a much more concentrated urine, ranging from 1,000 to 3,000 mOsm/L, compared to 100 to 500 for humans.

Animal tests have not proven whether the largely superfluous artificial sweetener is safe or not, but they have clearly shown that the tests themselves are undependable. They are also expensive. A single test of one product in one rodent species takes several years and costs well over one million dollars.

Takayama S, Sieber SM, Adamson RH, et al. Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. J Natl Cancer Inst. 1998;90:19-25.
Zurlo J, Squire RA. Is saccharin safe? Animal testing revisited. J Natl Cancer Inst. 1998;90:2-3.


A Drink May Be Good for Your Heart, But Raises Cancer Risk

Those having a drink or two a day in hopes of protecting their heart may find the remedy too good to be true. It has long been known that even one drink a day substantially increases a woman’s risk of breast cancer, and new evidence presents similar concerns about colon cancer.

Several epidemiologic studies have shown that alcohol (especially beer) consumption increases the risk of colon and rectal cancer. A new study of patients with a history of colon polyps, which are often harbingers of colon cancer, found that having seven or more drinks per week doubles the risk of recurrence.

Alcohol may do its dirty work by interfering with folic acid, a B-vitamin that helps repair damaged DNA. Alcohol, like smoking, reduces the amount of folic acid in the blood and blocks its biological actions.

IGF-1 and Prostate Cancer

Excessive levels of a natural com-pound in the blood, called insulin-like growth factor-1 (IGF-1), are linked to greater risk of prostate cancer. IGF-1’s natural function is to encourage cells to multiply. However, it also promotes aggressive cancer cell growth. It is already known to encourage breast cancer cell growth and is an even stronger cancer promoter than estrogen. A new study shows that men who have the highest levels of IGF-1 in their bloodstream have more than four times the risk of prostate cancer, compared to those with the lowest levels. Researchers are now considering using IGF-1 measurements in combination with prostate-specific antigen (PSA) to more precisely estimate cancer risk.

IGF-1 is produced in the liver and other tissues. It is also found in cow’s milk, which, after all, is designed by nature to foster rapid growth in a baby calf. Milk has IGF-1 levels ranging from 6 to 162 ng/ml, depending on whether it comes from a pregnant or postpartum dairy cow. IGF-1 may be the reason that several studies have linked milk consumption to cancer of the breast, prostate, and kidney.

Stress Lowers Immune Defenses against Cancer

Cancer patients are understandably stressed by their diagnosis and the rigors of treatment. A new study of a group of women undergoing treatment for breast cancer found that stress weakens their natural anticancer defenses. The participants filled out questionnaires that assessed their stress levels. At the same time, researchers drew blood samples and measured the ability of specialized white blood cells, called natural killer cells, to eliminate cancer cells. They found that the more stress the women had, the worse their ability to destroy cancer cells and the more unresponsive their immune systems were in general.

The good news is that stress-reduction training can strengthen immunity. Teaching progressive muscle relaxation to healthy adults in a retirement home boosted their natural killer cell activity by 30 percent.

Diet and exercise help, too. Vegetarians have double the natural killer cell activity compared to omnivores, and a new review of 16 research studies shows that regular exercise cuts both pre- and postmenopausal breast cancer risk by 12 to 60 percent. How much exercise do you need? Most studies that have found benefits favor vigorous exercise roughly three to four hours per week.

Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-1 and prostate cancer risk: a prospective study. Science. 1998;279:563-565.
Baron JA, Sandler RS, Haile RW, et al. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst. 1998;90:57-62.
World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, and the Prevention of Cancer: a Global Perspective. Washington, D.C., 1997, pp. 460-462.
Andersen BL, Farrar WB, Golden-Kreutz D, et al. Stress and immune responses after surgical treatment for regional breast cancer. J Natl Cancer Inst. 1998;90:30-36.
Gammon MD, John EM, Britton JA. Recreational and occupational physical activities and risk of breast cancer. J Natl Cancer Inst. 1998;90:100-117.


Artery Damage from Cigarettes May Be Permanent

Cigarette smoking promotes the growth of artery blockages and increases heart attack risk. Unfortunately, quitting may not entirely eliminate the adverse effects of smoking.

The Atherosclerosis Risk in Community (ARIC) study measured carotid (neck) artery blockages by ultrasound in 10,914 people in Minnesota, Maryland, Mississippi, and North Carolina. Repeat measurements three years later showed that those not exposed to tobacco smoke had the least growth in their artery blockages, 25.9 mm over the three-year period. Smokers were much worse off. Their blockages had grown by 43.0 mm. Exposure to passive smoking added an extra 6 mm of artery blockage growth, both for nonsmokers and past smokers. Those who had smoked previously but quit were still growing blockages at a rate faster than for never-smokers, with a 32.8 mm growth of their artery blockages.

Smokers with hypertension or diabetes had a much more pronounced effect of smoking, with blockage growth of 58.0 mm and 80.1 mm, respectively.

Bottom line: Quitting helps, but your arteries may never be the same.

Garlic Counteracts Age-Related Artery Stiffening

As we get older, the body’s main artery, the aorta, gradually loses its elasticity, becoming unable to expand with each pulse of blood. As the aorta stiffens, each pulse from the heart squeezes straight through the narrowed passage at high speed, stressing the arterial system.

Garlic may help preserve the aorta’s natural resilience. Dr. Harisios Boudoulas of Ohio State University collaborated with researchers in Mainz, Germany, in a study of people who took garlic powder supplements daily for two years. “The aortas of our 70-year-old subjects who took garlic were as elastic as the aortas of 55-year-old subjects who didn’t take garlic.” Overall, 300 mg of garlic each day reduced aorta stiffening by 15 percent.

Howard G, Wagenknecht LE, Burke GL, et al. Cigarette smoking and progression of atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study. JAMA. 1998;279:119-124.
Breithaupt-Grogler K, Ling M, Boudoulas H, Belz GG. Protective effect of chronic garlic intake on elastic properties of aorta in the elderly. Circulation. 1997;96:2649-2655.


Spring/Summer 1998

Spring/Summer 1998
Volume VII
Number 2

Good Medicine

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