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July 2001

What's Hot Archive


July 30, 2001

Oral contraceptives may not prevent ovarian cancer in women with mutation

The July 26, 2001 issue of New England Journal of Medicine published the results of a population based study indicating that oral contraceptives, currently known to reduce the risk of ovarian cancer, may not do so in women with the BRCA1 or BRCA2 genetic mutations. Mutations in BRCA1 (BRCA stands for breast cancer) and BRCA2 are associated with an increased risk of ovarian and breast cancer. Along with oral contraceptive use, having children also reduces the risk of ovarian cancer.

Eight hundred forty Israeli women with ovarian cancer or primary peritoneal carcinoma possibly of ovarian origin, and 751 women without cancer who served as controls completed interviews and underwent mutation analysis of BRCA1 and BRCA2 between 1994 and 1999. Of the controls, 1.7 percent had one of three mutations to BRCA1 or BRCA2 that are found commonly in Jewish populations, while 29% of those with ovarian cancer carried a mutation.

An analysis of the data adjusted for several factors revealed that ovarian cancer risk was lowered with the birth of each additional child. Oral contraceptive use for five or more years lowered the risk of ovarian cancer with each year of oral contraceptive use overall, but in carriers of one of the mutations to BRCA1 and BRCA2, the use of oral contraception was not found to be protective against ovarian cancer, with only a 0.2 percent reduction of risk per year of oral contraceptive use observed in this group.

The study's authors suggest using oral contraceptives for ovarian cancer prevention is premature in women with mutations that put them at risk, particularly since these women are at an increased risk of breast cancer.

July 27, 2001

Hypertension in young adults significantly increases longterm mortality risk

Although elevated blood pressure is a well known cardiovascular mortality risk factor for middle-aged and older individuals, hypertension as a risk factor in young adults has not been well studied. To this end, researchers studied 10,874 men between the ages of eighteen to thirty-nine, in an effort to determine the association between blood pressure and longterm mortality risk. The subjects were recruited from 1967 to 1973, as part of the Chicago Heart Association Detection Project in Industry . Results were published in the June 25, 2001 issue of Archives of Internal Medicine.

Participants were free of coronary heart disease or diabetes, and were not on antihypertensive medication. Blood pressure was measured at the beginning of the study and subjects were followed for an average of twenty-five years. Participants were classified as having blood pressure that was optimal, normal, high-normal, or stage 1 hypertension. During the follow-up period, seven hundred fifty-nine men died: two hundred fifty-seven from cardiovascular diseases.

The researchers found a continuous age-adjusted association of baseline systolic blood pressure to coronary heart disease mortality. Above-normal blood pressure was significantly related to increased longterm mortality from coronary heart disease, cardiovascular diseases, and all causes, compared to the group with normal blood pressure. Those with stage 1 hypertension had their life expectancy shortened by 4.1 years. Because blood pressure screening and treatment has focused on middle-aged and older individuals, this study reveals that such efforts should be directed toward younger people as well. The authors recommend that preventive measures be taken by this population and that efforts be made for early detection so that lifestyle changes can be implemented. These measures include weight control, exercise, avoidance of excessive salt, fat, and alcohol; ensuring adequate intake of potassium, and consumption of vegetables, fruits, grains, legumes and low fat protein sources.

July 25, 2001

American Heart Association issues statement against hormone replacement for heart attack prevention

In a scientific statement published in the July 24 2001 issue of Circulation: Journal of the American Heart Association, physicians were advised not to prescribe hormone replacement therapy for stroke and heart attack prevention in women with preexisting cardiovascular disease. The statement was issued partly as a result of the large-scale Heart and Estrogen Replacement Study (HERS) which found no benefit of hormone replacement for postmenopausal women with cardiovascular disease. The American Heart Association recommends controlling high blood pressure and elevated cholesterol with lifestyle changes and with medications if necessary, and that hormone replacement be used for noncardiovascular benefits.

The guidelines published in Circulation recommend that women who have had a stroke or heart attack not be prescribed hormone replacement therapy to prevent a second event. To prevent an initial event, the AHA recommends lowering cholesterol and blood pressure through smoking cessation, weight loss and increased exercise levels and/or with medication. They advise that women with cardiovascular disease who are on hormone replacement continue to use it based on their preferences and on its noncoronary benefits. Lead author of the advisory, Lori Mosca MD, PhD, director of preventive cardiology at New York Presbyterian Hospital of Columbia and Cornell universities commented, "For many years, cardiologists and other health care providers who take care of women have assumed that HRT protects the heart. At this time there is not sufficient evidence to make that claim - our purpose is to clarify the role of hormones in heart disease prevention." She stated that the benefits of hormone replacement therapy in postmenopausal women, such as preventing hot flashes and possibly preventing osteoporosis must be weighed against the risk of gallbladder disease, blood clots and breast cancer.

July 23, 2001

Low DHEA levels predict death in male smokers.

DHEA is a hormone secreted by the adrenal glands, whose levels may be correlated with longevity. Levels of the hormone are higher in men than in women and have been negatively correlated in men with increased short term mortality in one study. In another study, published in the July 3 2001 issue of Proceedings of the National Academy of Sciences, researchers utilized data from the PAQUID program, a prospective cohort study of 3,777 elderly individuals living in southern France. Six hundred twenty-two participants in the current study had their blood tested for DHEA sulfate at a one year follow-up, and 346 were tested after eight years, with 290 of these used in the statistical analysis. Participants were interviewed in order to obtain sociodemographic information, smoking status, wine consumption, physical activity and medical parameters such as current medication use, personal history of disease, physical function disability and subjective health perceptions. Cognitive function and depression were also assessed.

Interestingly, DHEA Sulfate levels were found to decline in two thirds of the subjects while increasing in the a third. The rise in DHEA could possibly be due to subclinical impairment of kidney and liver function, but this was not explored. The researchers found no correlation with health parameters collected initially and DHEA levels. However for men, the risk of death at ten year followup was doubled when the initial DHEA sulfate level was low. This risk increased for male smokers, with low DHEA sulfate levels emerging as a reliable predictor of death in this group. The authors question if tobacco could lower DHEA sulfate or if low DHEA sulfate levels are an indicator or potentiator of cardiovascular disease related to smoking.

The researchers concluded that DHEA appears to be less important in women than in men, which could be due to differing hormone metabolism, and that its low levels are a predictor of death in men, particularly for those who smoke. For male smokers with low DHEA levels, the authors recommend DHEA supplements as well as quitting smoking.

July 20, 2001

Folic acid improves endothelial function in coronary artery disease

A study reported in the Arteriosclerosis, Thrombosis and Vascular Biology, July 2001 issue, demonstrated a positive effect of folic acid on endothelial function in patients with coronary artery disease. The endothelium is the lining of the blood vessel that becomes dysfunctional with atherosclerosis. Homocysteine, a toxic amino acid that elevates cardiovascular disease risk, promotes endothelial dysfunction, possibly by its ability to generate reactive oxygen species, causing free radical damage. The B vitamin folic acid is known to lower homocysteine levels. The researchers in this study sought to determine the effect of a high dose of folic acid on endothelial function and its possible mechanism of action.

Fifty-two patients, aged 57 to 66, with coronary artery disease were given 5 milligrams folic acid per day for six weeks, and ten more were given intra-arterial 5-methyltetrahydrofolate, which is the principal circulating form of folic acid in the body. Endothelial function was assessed by flow-mediated dilatation, using ultrasound. Participants were tested for homocysteine, folate, lipids and other values. After six weeks of treatment with 5 mg folic acid, endothelial function significantly improved. Although homocysteine was lowered by an average of 19%, improvement in endothelial function was not correlated with homocysteine reduction. The subjects receiving 5-methyltetrahydrofolate had greatly improved endothelial function, without a change in homocysteine. In a separate in vitro experiment, 5-methyltetrahydrofolate prevented the increase in superoxide caused by homocysteine, an effect also seen in those receiving folic acid.

The researchers concluded that high dose folic acid benefits endothelial function in coronary artery disease, but does so independently of its effect on homocysteine. They speculate that the reduction of intracellular endothelial superoxide associated with folic acid supplementation may be responsible for its action. It was stressed that the dose of folic acid used was pharmacological, and one cannot assume that the benefits seen in this study would be seen with 400 micrograms per day folic acid supplementation or by an increased dietary intake.

July 18, 2001

Calcium and vitamin D supplements recommended for patients on corticosteroids

Corticosteroid (also known as glucocorticoid) drugs, such as prednisone and hydrocortisone, are prescribed for a number of conditions, including arthritis and allergies. While many physicians are aware that the use of these drugs increases the risk of fracture in postmenopausal women, few recommend measures to prevent this, or are aware that the drugs cause osteoporosis in premenopausal women and in men as well.

A committee of the American College of Rheumatology recently published an update to their 1996 report entitled, "Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis." In this updated report, the committee recommends that patients receiving glucocorticoid therapy receive bone mineral density testing at baseline and every six months to monitor bone loss.

A committee of the American College of Rheumatology recently published an update to their 1996 report entitled, "Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis." In this updated report, the committee recommends that patients receiving glucocorticoid therapy receive bone mineral density testing at baseline and every six months to monitor bone loss.

In addition to calcium and vitamin D supplementation, the committee recommends that patients on glucocorticoids stop smoking, reduce alcohol consumption and exercise. The addition of bisphosphonates will not only increase bone mineral density but help prevent the vertebral fractures commonly seen in this population.

July 16, 2001

Cognitive decline predicted by homocysteine levels

The Third International Conference on Homocysteine Metabolism in Sorrento, Italy was the site of the announcement by a research team from Wales that homocysteine levels are predictive of cognitive function decline. The research team, led by Honorary Research Fellow of the University of Wales College of Medicine, Dr Andrew McCaddon, followed up earlier research in 1998 in which they discovered elevated serum homocysteine levels in Alzheimer's patients. This research was confirmed in a separate study at Oxford University. It was not then known whether the elevation in homocysteine levels were caused by Alzheimer's disease or if they were an effect. The latest project shows that homocysteine levels are predictive of cognitive decline in healthy elderly individuals over a five-year period, with higher blood levels of homocysteine associated with a more rapid decline in cognitive function. These results indicate that high homocysteine levels are more likely to be cause than an effect of impaired cognitive function. The report will appear in the September 2001 issue of the journal Dementia and Geriatric Cognitive Disorders.

Homocysteine is a toxic amino acid which is a byproduct of methionine metabolism. It has been found to be elevated in cardiovascular disease, and is linked with an increased risk of heart attack and stroke.

Although homocysteine can be lowered by folic acid, TMG, vitamin B6 and vitamin B12, it is not known if taking these nutrients will be effective in preventing mental decline or Alzheimer's disease. Dr McCaddon, a general practitioner in North Wales, stated, "Although our results show that homocysteine levels in blood predict cognitive decline, it is not yet known whether reducing homocysteine slows down this process.

July 13, 2001

Free radical fighter studied

MetaPhore Corporation has developed a drug that mimics the effects of superoxide dismutase or SOD, one of the body's own highly potent antioxidants. The drug, M40403, was recently shown in an clinical trial to be safe and well tolerated. The trial was a first, as no small molecule drugs that imitate antioxidant enzymes have previously been tested on humans. Efficacy studies will follow.

Superoxide dismutase is an enzyme that scavenges the damaging superoxide radical. Superoxide has been found to be overproduced by the body in cancer and other diseases. The body's production of SOD subsequently becomes inadequate, allowing the superoxide radical to react with other molecules, damaging tissue.

The next study will utilize the drug in combination with interleukin-2 in patients with end stage kidney cancer and advanced melanoma. Studies in models of cancer have demonstrated that M40403 limits the drop in blood pressure caused by interleukin-2 and appears to increase its tumor-fighting ability. Side effects of high-dose interleukin-2 therapy can be life-threatening and usually require that the patient receiving it be treated in an intensive care unit. Some individuals are unable to complete their course of treatment.

MetaPhore's Vice President and Director of Pharmacology, Daniela Salvemini stated, "Based on these results, SOD enzyme mimetics may offer improved therapeutic options for end-stage cancer patients, with a greatly reduced side-effect profile. Moreover, these studies also indicate the drug may hold wider potential with other cytokine-based cancer therapies." Other preclinical studies have shown that the drug has further potential uses in the treatment of diseases involving free radical damage, including heart attack, stroke, pain and inflammation, and other types of cancer, as well as in the maintenance of vascular pressure.

July 11, 2001

Vitamin B6 inhibits breast cancer growth in vitro

Twenty years ago, research conducted on vitamin B6 showed that the vitamin interfered with estrogen-sensitive growth, but further research was not forthcoming until Barbara Davis, Assistant Professor of Human Nutrition, Foods and Exercise at Virginia Tech in Blacksburg, Virginia, received funding two years ago to pursue a study that examined the effect of vitamin B6 on estrogen receptor positive and estrogen receptor negative breast cancer cell lines in the presence or absence of estrogen. (The majority of breast cancers are fueled by the hormone estrogen.)

The study, published in the October 2000 issue of the journal Nutrition and Cancer, revealed that the pyridoxal form of B6 reduced the growth of cancerous tumors by 37% when estrogen was present, and that megadoses suppressed it by 85% in both cell lines. The vitamin was also able to suppress tumor growth in estrogen's absence, with an average 40% reduction observed with high doses and a 70% reduction with megadoses. Remarkably, this reduction in growth occurred within twenty-four hours of vitamin B6 administration. The vitamin's mechanism of action appears to be independent of an effect on estrogen.

Dr Davis cautioned, "The doses that we are working with at this time are not something that can be achieved by diet. The problem with B6 is that it can be toxic at high levels. People have been known to abuse it to treat carpal tunnel syndrome and PMS, and it results in numbness and tingling in the fingers, indicating that nerves in the extremities are affected." Davis would like to explore whether vitamin B6 could be used locally by implantation at a tumor site. Her newest research project will test a compound in vivo that has a pyridoxal-like structure but can be safely used by humans at the needed doses.

July 9, 2001

Prevention ignored in half of stroke and heart attack survivors

A study published in the July 9 2001 issue of Archives of Internal Medicine showed that many survivors of stroke and heart attack are not taking measures to prevent a second event. The study was conducted by researchers at the University of Buffalo Toshiba Stroke Research Center and Department of Neurosurgery who analyzed data collected from 17,752 people from 1988 to 1996 who took part in the National Health and Nutrition Examination Survey (NHANES III). NHANES was conducted by the CDC to estimate the prevalence of chronic disease and identify risk factors.

The data revealed that 53% of the 1,252 stroke and heart attack survivors who had uncontrolled hypertension prior to their cardiovascular event were still hypertensive after the event, and 46% who had high cholesterol previous to their heart attack of stroke failed to control it afterward. And as testimony to the power of addiction, 18% of smokers did not give up their habits.

University at Buffalo assistant professor of neurosurgery, Adnan I Quershi MD, stated, "Persons who have suffered a stroke or heart attack are at very-high risk for subsequent stroke or heart attack. The study raises important questions about the adequacy of secondary prevention in a population at very-high risk for subsequent cardiovascular events. This study lays the basis for developing programs aimed at preventing a second stroke or myocardial infarction in patients at very high risk. Such programs could significantly reduce the number of cardiovascular events and prevent a great deal of pain and suffering. First, physicians would have to accelerate their efforts in monitoring and treating cardiovascular risk factors in people who survive initial cardiovascular events. Second, patients must recognize the great risk they face of having another cardiovascular event and accept responsibility for reducing that risk."

July 5, 2001

Stroke survivors may need vitamin D

The July 2001 issue of Stroke: Journal of the American Heart Association, reported that the high incidence of hip fracture following a stroke could be prevented by vitamin D. Research has shown that the growing population of stroke survivors have double to quadruple the risk of hip fracture as that of stroke-free individuals.

In order to ascertain the effect of vitamin D on hip fractures in stroke patients, researchers from Japan tested individuals aged sixty-five and older who had hemiplegia caused by stroke for bone mineral density and levels of a byproduct of vitamin D metabolism called 25-hydroxyvitamin D, or 25-OHD. The subjects were also asked to complete a questionnaire concerning diet and sunlight exposure, so that the vitamin D intake of each could be calculated. Of the 236 participants, 88 were deficient in vitamin D as determined by serum 25-OHD levels, 76 had insufficient levels and 72 were considered to have sufficient amounts of the vitamin. During the two year follow-up period, the participants categorized as deficient had 7.1 times the amount of fractures as those whose levels were considered insufficient. All of those who experienced hip fractures in the deficient group had 25-OHD levels that were considered severely deficient, at half the upper level for inclusion in this group of 10 nanograms per milliliter. No patients with sufficient vitamin D levels and only one in the insufficient group experienced hip fractures.

The immobilization and older age of many stroke patients may be the cause for low 25-OHD levels. Because vitamin D is necessary for bone strength, a deficiency often leads to osteoporosis. With hip fracture the most dangerous of all fractures caused by osteoporosis, and vitamin D and calcium supplementation having been demonstrated to aid in their prevention in postmenopausal women, supplementation with these nutrients may be proven by future research to be a worthwhile prophylactic measure for stroke victims.

July 3, 2001

Successful frozen ovarian grafts in large animals a first

The annual meeting of the European Society of Human Reproduction and Oncology held in Lausanne, Switzerland this week was the site of the announcement that ovarian tissue was successfully removed from sheep, frozen and reimplanted back into the same animals, leading to live births. Professor Bruno Salle and Dr Jacqueline Lornage of the Hopital Edouard Herriot in Lyon, France, removed one ovary from each sheep, bisected it, and froze the tissue in liquid nitrogen for a period of one to three months. Dr Salle commented that the grafts could be stored for longer periods. After being thawed, incubated, and grafted back into the donor sheep, the ovaries regained normal function within two to four months, and the four of the six sheep became pregnant. Although three of the six lambs died after birth, Dr Salle believes this was a coincidence (one animal delivered twins prematurely), as none suffered from any malformations.

It is hoped that the technique can be perfected so that cancer patients facing a loss of ovarian function due to chemotherapy or radiation could have ovarian tissue frozen in advance of the procedures, in the event that they wanted to become pregnant in the future. This differs from having one's eggs frozen, which requires in-vitro fertilization. Professor Salle, of the Departmement de Medecine de la Reproduction at the Hopital Edouard Herriot stated , "These four pregnancies, after frozen ovarian autograft, give immense hope to women who become sterilised by cancer treatments. However we are not ready to try this technique in women yet, as first of all the procedure has to be repeated by ourselves and other researchers, and secondly, we need to discover how long the ovarian graft continues to function."

July 2, 2001

Cranberry vindicated in prevention of urinary tract infections

A recent review published in the medical literature indicated that an analysis of studies attempting to determine the preventive benefits of cranberry juice against urinary tract infection pronounced the evidence in cranberry's favor inconclusive. However, in a randomized trial published in the June 30 2001 issue of British Medical Journal, participants who drank cranberry juice experienced half the rate of urinary tract infection recurrence compared to the control group. A group receiving lactobacillus-containing beverages had approximately the same rate of reinfection as controls. (Lactobacillus applied locally has prevented recurrent urinary tract infections in some women.)

One hundred fifty Finnish women with a history of urinary tract infection caused by E coli who were not on antibiotics were randomized into three groups who received daily cranberry-lingonberry juice containing 7.5 grams cranberry concentrate, a lactobacillus-containing beverage five days per week, or no supplemental beverage for six months. After six months, 16% of those who received the cranberry-lingonberry concentrate experienced a recurrence of urinary tract infection, compared to 39% of those who received lactobacilli and 36% who received neither.

Women with previous urinary tract infections were chosen for the study because of the high incidence of recurrence in this population, necessitating prophylactic antibiotic use by some. By combating E coli bacteria in the stool, which is the source of infection, and by preventing the growth of this bacteria in the urine, oral consumption of cranberry juice can help prevent this painful condition, which effects up to 60% of all women at some point in their lives.

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