ABSTRACTS

COPENHAGEN, DENMARK. Medical researchers at the Nordic Cochrane Centre have reached the surprising conclusion that "screening for breast cancer with mammography is unjustified". The researchers reviewed eight randomized trials aimed at determining the effect of mammography screening on mortality from breast cancer. The trials carried out in the United States, Canada, Scotland, and Sweden involved over 500,000 women. A careful study of the design of the trials showed that six of them were biased in a direction which would tend to exaggerate the benefits of mammography. In some of the trials the women in the screening group were significantly younger than those in the control group. In others the screened women were in a significantly higher socio-economic stratum than the women in the control group. The researchers conclude that only two studies, the Canadian Mammography Screening Study and a study carried out in Malmo, Sweden were sufficiently unbiased to be of value. The pooled results of these studies showed no reduction in breast cancer mortality due to the use of mammography screening. The researchers back up their contention that mammography screening is unjustified by pointing out that there has been no decrease in breast cancer mortality in Sweden since the introduction of mammography in 1985.
The researchers conducted a more detailed analysis of the findings from the Malmo and Stockholm trials and found that women in the mammography groups were far more likely to have undergone surgery and radiotherapy than had women in the control groups. Dr. Harry J. de Koning of the National Evaluation Team for breast cancer screening in the Netherlands comments on the Danish report in an accompanying editorial. He believes there has been a reduction in breast cancer mortality in the UK due, in part, to the national breast screening program. About 800,000 women are screened every year in the Netherlands, but no statistically significant reduction in breast cancer mortality has been found in the first nine years of the screening program. Dr. de Koning concludes that we still need answers to the question "Are screening programmes justified and at what cost to women and to society?"
Gotzsche, Peter C. and Olsen, Ole. Is screening for breast cancer with mammography justifiable? The Lancet, Vol. 355, January 8, 2000, pp. 129-34
de Koning, Harry J. Assessment of nationwide cancer-screening programmes. The Lancet, Vol. 355, January 8, 2000, pp. 80-81 (commentary)

HAMILTON, ONTARIO, CANADA. Numerous studies suggest that a high intake of vitamin E is associated with a reduced risk of developing coronary artery disease and atherosclerosis. A group of Canadian researchers (Heart Outcomes Prevention Evaluation Study) now report that vitamin E supplementation does not retard or reverse existing heart disease. Their study involved 2545 women and 6996 men 55 years of age or older who had been diagnosed with diabetes or cardiovascular disease (80 per cent of the participants). The participants were given 400 IU of natural vitamin E or a placebo daily for a mean of 4.5 years. At the end of the study period 772 of the 4761 patients assigned to vitamin E and 739 of the 4780 patients assigned to placebos had suffered a stroke or a heart attack or had died from cardiovascular causes. There were no statistically significant differences between the number of heart attacks, strokes or cardiovascular deaths in the vitamin E group and the placebo group. There also were no significant differences between the two groups in the number of new cases of unstable angina, congestive heart failure, complications of diabetes, cancer or death from any cause. There were no significant adverse effects of vitamin E and no increase in hemorrhagic stroke in the vitamin E group. The researchers conclude that vitamin E supplementation has no beneficial effect on cardiovascular disease progression in a high-risk population. However, they do point out that their findings might have been different if the study period had gone beyond 4.5 years, if vitamin E had been given together with other antioxidants, and if the study population had not been at high risk even before the start of the study. NOTE: This study received funding from Negma, Hoechst-Marion Roussel, AstraZeneca, King Pharmaceuticals, the Medical Research Council of Canada, the Natural Source Vitamin E Association, and the Heart and Stroke Foundation of Ontario.
Yusuf, Salim, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. New England Journal of Medicine, Vol. 342, January 20, 2000, pp. 154-60

TAIPEI, TAIWAN. High blood levels of the amino acid homocysteine have been associated with an increased risk of atherosclerosis. Homocysteine is formed in the body from methionine (an amino acid found in proteins) in a process that can be blocked by folic acid and vitamins B6 and B12. High homocysteine levels can induce endothelial dysfunction (a narrowing of the arteries) which in turn is believed to be a precursor of atherosclerosis. Researchers at the National Taiwan University Hospital now report that homocysteine-induced endothelial dysfunction can be avoided or very significantly ameliorated by supplementing with folic acid and vitamins B6 and B12.
The study involved two men and fourteen women between the ages of 41 and 55 years. At the start of the study all participants had their blood levels of homocysteine and their blood flow through the brachial artery measured after a 10-14 hour overnight fast. They were then given an oral methionine loading test to simulate the intake of a high protein meal. Four hours later their average homocysteine level had increased from 7 micromol/L to 22.7 micromol/L and the blood flow (flow-mediated vasodilation) had decreased by 40 per cent. The experiment was repeated, but this time 5 mg of folic acid was given together with the methionine; the results were similar to those obtained in the first experiment indicating that folic acid does not act immediately as an "antidote" to a high intake of methionine. The participants were then given 5 mg of folic acid, 100 mg of vitamin B6, and 0.5 mg of vitamin B12 daily for five weeks. At the end of the five weeks their average homocysteine level had decreased to 5.2 micromol/L. The methionine loading test was repeated. Four hours later the average homocysteine level among the participants had increased to 17 micromol/L, but there was no statistically significant difference in blood flow before and after the methionine loading test. The researchers conclude that short-term (five weeks) administration of folic acid and vitamins B6 and B12 will reduce post-methionine load homocysteine levels and eliminate or ameliorate endothelial dysfunction (an early manifestation of atherosclerosis).
Chao, Chia-Lun, et al. Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia. American Journal of Cardiology, Vol. 84, December 1, 1999, pp. 1359-61

BERLIN, GERMANY. St. John's wort (hypericum extract) is the most widely prescribed antidepressant in Germany and is gaining increased popularity in North America. German medical researchers have just released the results of a major study which shows that hypericum extract is effective in reducing moderate depression. The trial involved 66 men and 197 women who had been diagnosed with moderate depression. The patients were randomized to receive hypericum extract (350 mg of STEI 300 three times daily), a placebo or 100 mg of the tricyclic antidepressant imipramine (Tofranil) daily for eight weeks. Their depression score was measured using the Hamilton depression rating scale (and other scales) at the start of the study period and after 1, 2, 4, 6 and 8 weeks. Evaluation of the scores at 6 and 8 weeks showed that hypericum was significantly more effective than the placebo and as effective as imipramine in reducing depression. Side effects were more frequent in the imipramine group (46 per cent) than in the hypericum group (22 per cent), and the placebo group (19 per cent). The researchers conclude that the hypericum extract used in the study is effective in reducing mild to moderate depression, but warn that the findings may not be directly applicable to other hypericum extracts as there is a great variation in the concentration of active components. The STEI 300 brand used contains 0.2 to 0.3 per cent hypericin and pseudohypericin and 2 to 3 per cent hyperforin. NOTE: This study was funded by Steiner Arzneimittel, the manufacturer of STEI 300.
Philipp, Michael, et al. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. British Medical Journal, Vol. 319, December 11, 1999, pp. 1534-38
Linde, Klaus and Berner, Michael. Has hypericum found its place in antidepressant treatment? British Medical Journal, Vol. 319, December 11, 1999, p. 1539 (commentary)

SEATTLE, WASHINGTON. It is estimated that almost 180,000 American men will be diagnosed with prostate cancer in 1999. More than 70 per cent of these cancers will be localized and will be treated with radical prostatectomy (removal of the prostate gland) or radiation or in some cases will be left alone and watched carefully for further growth (expectant management). The most commonly chosen option is radical prostatectomy. It has long been known that this surgery can have serious after effects specifically impotence and incontinence. However, what has been less clear is just how frequent these complications are.
Researchers at the Fred Hutchinson Cancer Research Center have just released the results of a major study which paints a grim picture of the seriousness and frequency of the after effects of radical prostatectomy. The study involved 1291 black, white, and Hispanic men between the ages of 39 and 79 years who had been diagnosed with localized prostate cancer between October 1, 1994 and October 31, 1995. All the men had undergone radical prostatectomy within six months of diagnosis. The men completed questionnaires or had personal interviews about their urinary and sexual functions at baseline and 6, 12 and 24 months after diagnosis.
At 18 or more months following surgery 59.9 per cent of the men were impotent and 38.9 per cent reported involuntary urination (incontinence) at least once a day. Only 37.8 per cent of the men reported no problems with incontinence and only 14 per cent reported no problem with sexual function. Prior to surgery 77.8 per cent reported no problem with incontinence and 50.3 per cent reported no problem with sexual function. The after effects of prostatectomy were less pronounced among younger men and among men with higher education and higher income. The decline in sexual function was most pronounced among white men and least pronounced among black men. Nerve-sparing surgery improved the outcome somewhat with 65.6 per cent of men having non-nerve-sparing surgery being impotent after 18 months as compared to 56 per cent among men having had bilateral nerve-sparing surgery. Surprisingly, 75.5 per cent of the men were satisfied with their surgery and 71.5 per cent said that they would choose radical prostatectomy again.
Stanford, Janet L., et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer. Journal of the American Medical Association, Vol. 283, January 19, 2000, pp. 354- 60

ALBANY, NEW YORK. Rheumatoid arthritis is a systemic inflammatory disease involving an excessive release of leukotriene B4 and interleukin 1 in the body. Both animal experiments and human studies have shown that supplementation with fish oils reduces the release of these inflammatory compounds and in the process relieves the common arthritis symptoms of morning stiffness and tender joints. Dr. Joel Kremer of the Albany Medical College has summarized the current knowledge concerning fish oils and rheumatoid arthritis and concludes that taking 3-6 grams daily of fish oils (n-3 dietary fatty acids) for 12 weeks or more will significantly diminish joint pain and morning stiffness in RA patients. Several studies have shown that the improvement in some patients is significant enough to allow them to materially reduce or completely discontinue their use of non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac and naproxen. Dr. Kremer also points out that fish oil supplementation has been found to benefit patients with inflammatory bowel disease.
Kremer, Joel M. n-3 fatty acid supplements in rheumatoid arthritis. American Journal of Clinical Nutrition, Vol. 71 (suppl), January 2000, pp. 349S-51S

BERN, SWITZERLAND. The energy required for short-term muscular exertion is derived from phosphocreatine and the availability of it is a limiting factor for the duration of high-intensity exercise. The availability of phosphocreatine in turn depends on an adequate store of creatine in the muscles. It is therefore not surprising that several trials have shown that supplementation with creatine can markedly increase short-term athletic performance.
Researchers at the University of Bern now report that athletes can increase their short-term physical performance by as much as seven per cent through creatine supplementation. Their study involved 10 well-trained male physical education students. They took 20 grams/day of creatine monohydrate or placebo for five days; they then went through a washout period (average duration - 61 days, minimum duration - 28 days) after which the students who had taken the placebo were given creatine and vice versa. The physical performance of the students was measured before and after supplementation using a bicycle ergometer. The test regimen consisted of 10 repetitive sprints of six seconds each with a 30- second rest period between each sprint. The researchers found that the study participants who had taken creatine were able to cycle an average of seven per cent faster on the last sprints (sprints 8-10) than were the students on the placebo. The creatine group also produced less blood lactate during the exercise, had more creatine in the urine, and more creatine and creatinine in the blood serum. Creatinine level in the urine and creatinine clearance were not significantly different in the two groups. The researchers conclude that short-term supplementation with creatine monohydrate is effective in improving short-term physical performance and shows no detrimental side effects. NOTE: This study was partially funded by Wander AG, a Swiss manufacturer of creatine.
Kamber, Matthias, et al. Creatine supplementation - Part I: performance, clinical chemistry, and muscle volume. Medicine & Science in Sports & Exercise, Vol. 31, December 1999, pp. 1763-69

MELBOURNE, AUSTRALIA. Many women over 50 years of age are prescribed hormone replacement therapy (HRT) in order to ameliorate menopause symptoms and prevent excessive loss of bone mass. Unfortunately, HRT has been associated with an increased risk of breast cancer. It is therefore important that women on HRT be checked for breast tumors at periodic intervals. Public health authorities in most developed countries recommend screening with mammography every one or two years for women over the age of 50 years. Australian researchers now report that mammography is less accurate in women on HRT than in women not on HRT. Their study involved 103,770 women in the state of Victoria who had a mammogram for the first time in 1994. The use of HRT among these women varied from 20.2 per cent in those aged 40-49 years to almost 40 per cent in women aged 50-59 years. The detected incidence of breast cancer among women in the 50-59 year age group was 0.33 per cent (141 cases out of 43,090) for women not on HRT as compared to 0.58 per cent (100 cases out of 17,209) for women on HRT. Unfortunately, the sensitivity of the screening was found to be significantly poorer in the case of women on HRT. In the age group 50-69 years (the most vulnerable group) the sensitivity (percentage of actual cancers detected) of mammography was only 64.3 per cent among HRT users as compared to 79.8 per cent among non-users. So not only does HRT use increase the risk of breast cancer, but it also makes it significantly harder to detect. The researchers suggest that women on HRT may wish to discontinue therapy for a brief period before mammography and also recommend that women be told about the lack of accuracy of mammography in HRT users when they are faced with the decision about whether to start HRT.
Kavanagh, Anne M., et al. Hormone replacement therapy and accuracy of mammographic screening. The Lancet, Vol. 355, January 22, 2000, pp. 270-74

DETROIT, MICHIGAN. Researchers at the Henry Ford Health System, a large integrated health care network in the Detroit area, report that certain dietary factors are significantly associated with an increased risk for Parkinson's disease (PD). Their study involved 126 people who had been diagnosed with PD during the period April 1991 to July 1995 and 432 controls matched for sex and age. All participants completed a food frequency questionnaire which was reviewed with an interviewer as part of subsequent face-to-face interviews. The researchers found no statistically significant differences among cases and controls in the intake of vitamin E, vitamin C, vitamin A or beta-carotene. However, they did discover that people with a high intake of fat had twice the risk of developing PD as did people with a low intake. A high intake of cholesterol also doubled the risk while a high intake of lutein was found to increase the risk by a factor of 2.5. A high intake of iron was also found to be detrimental with PD cases having a median intake of 11.6 mg/day as compared to 10.1 mg/day for controls. The researchers note that a high intake of lutein has been found to protect against cancer and that PD patients tend to have a lower incidence of cancer. The researches conclude that a high dietary intake of fat, cholesterol, lutein, and iron may be associated with an increased risk for Parkinson's disease.
Johnson, C.C., et al. Adult nutrient intake as a risk factor for Parkinson's disease. International Journal of Epidemiology, Vol. 28, December 1999, pp. 1102-09

ANN ARBOR, MICHIGAN. Dr. Randolph Nesse MD, a psychiatrist at the University of Michigan, presents compelling evidence that minor depression (low mood) may actually be an adaptive condition which helps us avoid larger calamities than the ones that actually caused the depression. Dr. Nesse points out that manifestations of disease can arise either from a defect in the body's machinery or as a defensive mechanism. Examples of defects are jaundice and seizures which have no useful purpose. Pain, nausea, diarrhea, and fever, on the other hand, are useful defense mechanisms. He believes that, while major depression may well involve a defect, many cases of minor depression or low mood are actually defense mechanisms. Low mood tends to be accompanied by pessimism and lack of motivation. This may prove to be an advantage when it would be futile to try to correct the situation which gave rise to the depression in the first place. For instance, it may be better to do nothing than to challenge authority; it may be better to "lie low" if efforts to pursue an unreachable goal is likely to result in bodily damage, danger or at best, wasted effort. In the case of marital problems it may be better, at least for a while, to do nothing rather than to rush into a divorce.
Dr. Nesse also suggests that low mood is largely caused by a mismatch between achievements and expectations. It is therefore not surprising that minor depression is common among people who are anxious, duty-bound, ambitious, or lacking alternatives. Such people are often unable to disengage from unreachable goals and low mood may help them do so. Just as anxiety inhibits us from engaging in dangerous actions so minor depression may inhibit us from engaging in or continuing futile actions.
Nesse, Randolph M., Is depression an adaptation? Archives of General Psychiatry, Vol. 57, January 2000, pp. 14-20

HELSINKI, FINLAND. Inflammation and infection have been implicated as causative factors in atherosclerosis and heart attack (myocardial infarction). Researchers at the National Public Health Institute have just released a major report which confirms the connection and actually pinpoints the specific bacteria and viruses most likely to be involved. The study consisted of 241 white, middle-aged men with high cholesterol levels who had either suffered a heart attack or died from coronary heart disease during an 8.5-year period. The cases were matched with 241 controls who had not had any heart problems during the same period. Blood samples taken at baseline were analyzed for antibodies to common bacteria and viruses; the level of C-reactive protein (CRP), a systemic marker for inflammation, was also measured.
The researchers conclude that high levels of antibodies to the bacterium Chlamydia pneumoniae and the herpes simplex 1 virus are associated with an increased risk of heart attack and coronary death. They found no correlation between the antibody levels to adenovirus, cytomegalovirus, enterovirus, and Helicobacter pylori and the risk of heart disease. The level of CRP was found to be significantly higher in the cases than in the controls and a combination of high CRP levels and a high level of antibodies to the herpes virus conferred a 25-fold increase in risk. Smoking further increased the risk associated with Chlamydia and herpes infections especially in the case of Chlamydia infection.
Roivainen, Merja, et al. Infections, inflammation, and the risk of coronary heart disease. Circulation, Vol. 101, January 25, 2000, pp. 252-57

NEWSBRIEFS

Scientists harassed by pharmaceutical companies.
Dr. David Hailey of the Alberta Heritage Foundation for Medical Research voices concern over increasing evidence that manufacturers of pharmaceuticals are using their considerable clout to suppress the release of information detrimental to their products and even threaten scientists with legal action if they say anything unfavourable about them. Dr. Hailey points out that the majority of drug research in Canada is now funded by the private sector. Other researchers have noted that the publications of research studies funded by pharmaceutical companies is becoming increasingly biased with favourable results being widely and quickly publicized while negative results are being published slowly or not at all. In a recent case involving the stomach antacid omeprazole (Losec) the manufacturer, AstraZeneca, even went so far as to threaten a physician at McMaster University with legal action if she published the results of an Ontario Ministry of Health investigation which showed that Losec, although more expensive, was no more effective than other drugs in its class.
Hailey, David. Scientific harassment by pharmaceutical companies: time to stop. Canadian Medical Association Journal, Vol. 162, January 25, 2000, pp. 212-13

Is coffee bad for you?
The debate over the health effects of coffee and other caffeine-containing beverages continues unabated. Some researchers feel that coffee and its cousins are relatively harmless while others maintain that they are addictive drugs. Says Roland Griffiths, an expert on caffeine at the Johns Hopkins Medical Institutions, "caffeine is a drug and produces withdrawal effects." Withdrawal symptoms can occur in people who have as little as one cup of decaffeinated coffee a day and include headaches, fatigue, difficulty concentrating, and drowsiness. Many people develop a tolerance to caffeine and have no problem sleeping after drinking coffee while others not used to a regular caffeine intake become nervous and jittery and have trouble sleeping even after consuming relatively small amounts. Smokers tend to drink more coffee than non-smokers and if they quit smoking, but continue to drink coffee may become jittery and nervous making it more difficult to stay off the cigarettes. Dr. James Lane of Duke University Medical Center has shown that the caffeine in four or five cups of coffee not only increases the level of stress hormones in the body, but can also raise blood pressure by about five points. Other studies have found that even low doses of caffeine can change a fetal heart rate although the mother feels no effect. Dr. Griffiths goes on to say "If I have a message it's that people should know that caffeine is a drug and that they should treat it with respect."
Storm in a coffee cup. New Scientist, January 29, 2000, pp. 28-31

Health check on the Web.
University and many high school athletes are usually subjected to a preparticipation medical examination to ensure that they are healthy enough to participate in vigorous sports. Researchers at Stanford University have now developed a web-based comprehensive medical questionnaire (www.stanford.edu/dept/sportsmed/) which students complete before seeing the physician. The questionnaire covers such aspects as medical and musculoskeletal history, eating habits, menstrual and sleep disorders, stress, and health risk behaviours. Sixteen physicians used the results of the questionnaire in their examination and 15 of them found improvement in providing overall medical care; 13 noted a significant decrease in the time required to carry out each examination. The questionnaire demonstrated a 97 per cent sensitivity in detecting areas requiring physician attention and was deemed to be "easy" or "moderately easy" to complete by over 90 per cent of the athletes who used it.
Peltz, Julie E., et al. A comprehensive and cost-effective preparticipation exam implemented on the World Wide Web. Medicine & Science in Sports & Exercise, Vol. 31, December 1999, pp. 1727- 35

Coffee gets the lead out.
Many cities, particularly in the developing world, have high levels of toxic metals such as copper and lead in their water supply. Australian researchers now report that coffee made from contaminated water is essentially free of these pollutants. They found that the process of dripping hot water through the ground coffee removed up to 90 per cent of the copper and lead dissolved in the water. John Bisby, a consultant in environmental and occupational medicine in Melbourne, points out that drinking more coffee is not a practical way to combat water pollution. Says he "You can't drink all your water as coffee or you will have other side effects that are a lot worse than lead."
There's nothing like a good brew for cleaning up drinking water. New Scientist, February 12, 2000

Brain cells do grow back.
It has long been medical dogma that brain cells (neurons) do not regenerate and that humans (and other primates) are born with a given number of brain cells which have to last a lifetime. Even the discovery that mice, birds, and some monkeys grow new brain cells in adulthood has not changed this belief. Now a team of researchers from the Salk Institute in California and the Sahlgrenska University Hospital in Sweden reports that humans do indeed produce new brain cells well into adulthood. The new brain cells develop primarily in the hippocampus, a region of the brain involved in learning and memory. It appears that an abundant supply of serotonin (the "good mood" hormone) enhances the growth of new neurons while an excess of stress hormones (corticosteroids) stunt neuron birth and survival.
Grow your own. New Scientist, February 12, 2000