| August 2000 What's Hot Archive
August 30, 2000 Beta blocker improves heart failure survival by 35% The 22nd Annual Congress of the European Society of Cardiologists was the site of the announcement that the COPERNICUS, or Carvedilol Prospective Randomized Cumulative Survival Trial, had been halted due to signficant survival benefits seen in patients with advanced heart failure who used the beta blocker carvedilol, or Coreg R. After twenty-nine months, study participants on Coreg had 35% lower mortality rates than those on the placebo. The study's Data and Safety Monitoring Board recommended the study be halted so that the lifesaving benefits of the drug would not be withheld from the other patients. The trial was the first major international study involving treatment of advanced heart failure with a beta blocker, and included more than 2,200 patients conducted in twenty-one countries. Patients were enrolled who had advanced heart failure who did not require intravenous treatment or intensive care unit support, but who were taking such medications as ACE inhibitors, diuretics and digoxin.
Heart failure can result from hypertension, heart attack or diabetes, which weaken the heart so that blood is not circulated efficiently. Cases of heart failure are increasing, causing 250,000 fatalities each year, that number twice as high as 1979's figures. Coreg is the first beta-blocker proven to improve survival in patients with advanced heart failure, and is currently the only beta-blocker approved for mild to moderate heart failure. Milton Packer, M.D., Director, Heart Failure Center and Professor of Medicine, Columbia University College of Physicians and Surgeons in New York, and Steering Committee Chairman stated, "Until recently, most of the trials that had been conducted with beta blockers were in patients who had mild to moderate disease. There was a lot of fear that these drugs would not work in patients with advanced disease. The COPERNICUS trial is so important because the results tell us that carvedilol can reduce the risk of death in a much broader range of patients than we previously thought possible for agents with beta blocking activity."
—D Dye
August 28, 2000
Immune system can be rebuilt in lupus patients The current issue of The Lancet featured an article on a breakthrough treatment for people suffering from severe systemic lupus erythematosus. Lupus is an autoimmune inflammatory disease that can be fatal, producing inflammation of the brain, heart, lungs and kidneys in severe cases. Even in its mild manifestation, lupus can be disabling. In lupus, the immune system, which normally protects the patient, attacks the patients' own tissues.
The disease is currently treated with the drug cyclophosphamide, however some patients continue to experience organ dysfunction despite treatment, which puts them in danger. Researchers at Northwestern University in Chicago tested the combination of chemotherapy to suppress the immune system and the infusion of stem cells in seven patients. At two year follow-up, all seven were free of signs of active lupus, with all physiological markers having normalized.
The stem cells were taken from each patient, treated and reinjected, in order to rebuild the patients' immune systems following the chemotherapy. Lead study author Dr Ann Traynor commented, "What is exciting about this observation is that it appears that the immune system can correct its errors if early stem cells are allowed to mature as naive cells in a 'neutral' environment. This new generation of immune cells is not destined to repeat the ruinous errors of the prior generations. This observation may have implication for the therapy of many immune disorders including multiple sclerosis, myasthenia gravis, and even some types of cancers."
The study authors stress that the permanence of the results seen so far remains to be seen.
—D Dye
August 25, 2000
Hypertension diet lowers homocysteine After years of neglect by the medical establishment, homocysteine levels have finally been given the attention they deserve as a risk factor in cardiovascular disease. In a study funded by the National Heart, Lung and Blood Institute published in the August 22 issue of Circulation: Journal of the American Heart Association, a diet designed to treat high blood pressure was also found to lower homocysteine. The DASH diet, which stands for Dietary approaches to Stop Hypertension, used in the DASH trial, is a lowfat, low cholesterol and low saturated fat diet, abundant in vegetables, fruits and lowfat dairy foods, and which also includes nuts, grains, poultry and fish.
While several studies have confirmed the benefit of dietary supplements in lowering homocysteine, the researchers sought to determine what effect diet might have. During the eight week study, 118 study participants at four centers were offered either the DASH diet, the standard American diet or the standard American diet plus plenty of vegetables and fruits. While those on the standard American diet experienced a rise in homocysteine as compared to baseline levels, those receiving the DASH diet had lower homocysteine levels, as well as lower blood pressure. The group receiving the American diet plus fruits and vegetables experienced a smaller elevation in homocysteine than did the group receiving the American diet alone. It was observed that lower homocysteine levels correlated with levels of folate, also known as folic acid, a vitamin found in leafy green vegetables, among other foods.
This study demonstrates the importance of diet in the prevention of diseases related to elevated homocysteine, such as heart disease, peripheral vascular disease and stroke, as well as in the prevention of hypertension. Fruits and vegetables are also known for their cancer preventive benefits.
—D Dye
August 23, 2000
Aggressive men have aggressive immune systems A study in the most recent issue of Psychosomatic Medicine, conducted by researchers from Penn State and the University of Nebraska, correlated moderate aggression in men with an enhancement of immune function. A total of 4,415 men aged thirty to forty-eight were interviewed to determine their levels of aggression. Test subjects were questioned on their participation in various aggressive acts, such as "playing hooky" on occasion, being in fights, or having been in trouble with the law. Blood was taken from each participant to measure the types of white blood cells, and the participants received medical exams to ascertain their state of health.
The researchers found that thirty-nine percent of the respondents indicated that they had participated in two aggressive acts. This group had a 30 percent greater chance of being in the top quartile of CD4 cell numbers than those who reported no acts. These subjects also had higher B lymphocytes. These specialized white blood cells control antibody production and secrete signals that activate or deactivate immune response. Those reporting higher levels of aggression did not improve their chances of being in the top quartile, which led the researchers to conclude that it is moderate aggression that is associated with enhanced immune function.
Study coauthor Alan Booth, Distinguished Professor of Sociology and Human Development and Family Studies at Penn State commented, "Our study suggests that differences in people's aggressive behavior influences how their immune systems are prepared to deal with infections, viruses and bacteria. However, higher levels of aggression do not convey additional immune benefits . . . The strength of the finding is that we controlled for all types of factors that could impact the subjects' immune systems, such as whether the subjects smoked or consumed alcohol, their level of health and their testosterone scores." The researchers theorized that aggression has an evolutionary advantage, but can lead to trauma or exposure to new diseases, leading to the evolvement of a more competent immune system in men who were aggressive.
—D Dye
August 21, 2000
Sleep quality correlates with low GH in middle-aged men A series of studies conducted between 1985 and 1999 at four laboratories which examined 149 men ages 16 to 83 with no history of sleep disorder was analyzed this week in the Journal of the American Medical Association. The objective of the study was to determine the changes that occur with age in the quality and length of sleep, and their relationship to growth hormone (GH) and cortisol levels. Sixty to seventy percent of the growth hormone release that occurs each day happens during early slow wave (non-rapid eye movement) sleep. A frequent complaint of older individuals is poor sleep, and individuals in this age group have lower levels of growth hormone. Cortisol is a hormone that increases with stress and aging, with damaging effects.
Researchers found that from midlife until their seventies, the individuals examined lost an average of twenty-seven minutes sleep per night each decade. Deep, slow-wave sleep decreased from an average of 18.9% of sleeping hours during early adulthood, classified here as ages 16 to 25 years, to 3.4% during midlife (ages 36 to 50 years), and was replaced by lighter sleep. A decline in growth hormone release paralleled this decrease in slow-wave sleep.
The men's evening cortisol levels increased with age to become significant after the age of fifty. It is at this age that REM (rapid eye movement) sleep declines. Lower amounts of REM sleep were correlated with higher evening cortisol levels in this study.
The study authors hope that further research will be done in this area, and postulate that therapies designed to aid in the quality of sleep could have a beneficial affect on hormones, particularly on improving growth hormone release and lowering cortisol.
—D Dye
August 17, 2000
Zinc lessens common cold symptoms Zinc has been touted as a preventive and treatment for common cold based on the results of five positive clinical studies. However, five studies which showed no results when zinc was tried with cold sufferers has led some to question zinc's efficacy. Zinc defenders have argued that the zinc dose used in the negative trials was inadequate to produce results. A study published in Annals of Internal Medicine August 15 issue examined the effect of zinc on fifty individuals who were recruited within twenty-four hours of contracting colds. The participants received lozenges containing 12.8 mg zinc from zinc acetate, which they were instructed to take every two to three hours, or a placebo. This provided the zinc takers with approximately 80 mg zinc per day, which is more than five times the recommended daily allowance of 15 mg per day. The acetate form of zinc was chosen because it releases 100% of its zinc as zinc ions when consumed, making it highly bioavailable.
Those receiving zinc supplements had an average duration of 4.5 days of cold symptoms, compared to an average of 8.1 days experienced by those receiving a placebo. The group receiving zinc had a shorter duration of nasal discharge and suffered half the amount of days of cough than did the placebo group. Total overall symptoms, such as hoarseness, sneezing and sore throat were rated lower in severity by those receiving zinc.
Addressing the concern that high doses of zinc could cause a copper deficiency, the authors noted that a high dose of zinc would need to be consumed for six to eight weeks for it to occur.
Cold symptoms resemble the effects of proinflammatory cytokines, and can be thought of as an inflammatory cytokine disease, according to the study's authors. These cytokines may have been modulated by the rise in plasma zinc that occurred in the group receiving zinc supplementation, although the authors do not rule out the possibility of zinc having a direct antiviral effect.
—D Dye
August 16, 2000
Stenting plus super-aspirin better than clot-busting Heart attack, or myocardial infarction, occurs when a blood clot lodges in an artery that feeds the heart muscle, and causes death to the segment of the heart muscle that does not receive circulation. Because of the lack of clinical evidence indicating that other methods could be more effective and because of the wide availability of clot-busters, their administration has become the method of choice in treating patients with acute myocardial infarction.
A study of heart attack patients conducted between December 1997 and August 1999 was published in August 10 New England Journal of Medicine which compared the results of administration of a clot-busting drug, to those of inserting a stent and administering the drug abciximab, which is a blocker of platelet glycoprotein IIb/IIIa receptors, called a "super-aspirin". The study randomized 140 patients presenting with myocardial infarction into two groups: one receiving the stent with administration of abciximab and one receiving the clot-buster alteplase. All of the patients received aspirin and heparin immediately upon admittance to the emergency room. Sixty-nine patients received an infusion of the clot-busting agent altepase, while coronary stents were implanted in seventy-one patients who also received abciximab plus heparin.
Clinical evaluation showed that the amount of heart muscle salvaged in patients who received the stents was greater than in those who received the clot-blusting agent. After six months, patients who received stents had an 8.5% risk of second heart attack or death, compared to a 23.2% risk in the group receiving altepase.
The study authors have not determined how much administration of the drug abciximab contributed to the positive results of the group receiving the stents, and recommend further studies.
—D Dye
August 14, 2000
Drug combination to be tried with hepatitis C, cancer Maxim pharmaceuticals and Hoffman-Laroche have agreed to collaborate on clinical trials of the drugs Maxamine and Hoffman-Laroche's interferon-alpha, to be used against hepatitis C and cancer. Currently, interim results from a hepatitis C study showed that the drug combination led to a complete viral response in 69 percent of all patients. Interferon-alpha alone normally provides a 29 percent or less response. Maxamine is designed to reverse the immune suppression that can occur in cancer and chronic infectious diseases. This reversal allows therapies such as interferon-alpha to be more effective. The drug works by binding to the type 2 histamine receptor on the surface of phagocytes (a type of cell found in large quantities in tumors) which blocks their production of Reactive Oxygen Metabolities (ROMs) such as hydrogen peroxide. Reactive Oxygen Metabolites cause self-destruction of T cells and natural killer cells, which are immune system cells that are activated by cytokines such as interferon-alpha or interleukin 2. These immune system cells are active against tumor cells as well as virally infected cells such as those infected by hepatitis C.
By combining Maxamine with a cytokine such as interferon-alpha, the effectiveness of the cytokine is improved so that less is needed, and the patient therefore experiences less of their side effects.
The phagocytes' destruction of immune cells that would normally benefit from cytokines may be why cytokines have shown disappointing results when used against cancer and infectious diseases. The combining of a cytokine such as interferon-alpha with a pharmaceutical agent designed to protect the immune cells activated by the cytokine, may show real benefit in the treatment of many cancers and infectious diseases.
—D Dye
August 11, 2000
Bacteria suspect in Crohns's disease
The July issue of the journal Gastroenterology reported on the discovery by researchers at UCLA and Cedars-Sinai Medical Center, Los Angeles, of evidence of a bacteria in the affected areas of Crohn's disease. Crohn's disease is an incurable, chronic intestinal disorder, in which sufferers develop a weak and inflamed gastrointestinal tract, which causes severe abdominal pain and diarrhea. This leads to many related complications and increases the risk of colorectal cancer. The cause of Crohn's is unknown, but the disease has been believed to be an autoimmune disorder, in which the body attacks itself.
The researchers in this report examined intestinal lesions from 212 patients. They analyzed lesions caused by the disease and compared them to other intestinal mucosal tissue. A specific bacterial genetic sequence was present in 43% of the Crohn's lesions compared to being found in 5% of specimens derived from patients with noninflammatory bowel disease lesions and 9% of ulcerative colitis specimens. Antibodies to the sequence were also much higher in the serum of Crohn's disease patients than in other patients examined.
The method used in the study looked for DNA segments from a bacteria found in Crohn's patients, but the researchers as yet have not identified the bacteria. It is possible that it is one that is well known, or it could be a new discovery. It is not known yet whether this bacteria is the cause of disease, but researchers hope to pinpoint its identity so that therapies can be developed that will target it.
This research indicates that the body's immune response to a microorgansim could be the culprit in Crohn's. In the same issue of Gastroenterology, Dr Charles O Elson commented, "It seems likely that many antigens and microorganisms will be involved in stimulating the inflammation."
—D Dye
August 9, 2000
Smokers who quit lessen cataract risk
Cigarette smoking is a known risk factor in the development of cataracts. To determine whether smokers who have quit also have fewer cataracts, researchers examined 20,907 American physicians who took part in the Physicians' Health Study I, and who were cataract free at the beginning of the study. The study, published in the August 9 issue of the Journal of the American Medical Association, began in 1982 and followed the participants for an average of 13.6 years. Half the physicians at the beginning of the period had never been smokers, while 39% had quit and 11% were currently smoking. Those who were smokers were calculated to have twice the cumulative dose of smoking, which is the measurement of the amount of cigarette smoking that one has done over a lifetime, than did those who had quit. During the follow up period, 2074 diagnoses of age related cataract were made, and 1193 cataracts were removed. The study determined that the risk of developing cataract was approximately 20% lower in those who had quit smoking less than ten years prior to the development of cataract than in those who currently smoked, and even lower in those who had quit smoking more than ten years ago, when adjustments were made for age and other risk factors.
The lowest risk was experienced by those who had never smoked. In the first five years of follow up, study participants who smoked twenty or more cigarettes per day had twice the risk of cataract as this group.
Analysis of the data primarily indicated that although some damage caused by smoking is reversible, smokers who had quit experienced a lesser risk of cataract due to a lower cumulative dose of cigarette smoke.
—D Dye
August 7, 2000
Early high fat diet may increase Alzheimer's risk The World Alzheimer's Congress 2000 held last month was the site of a report presented by researchers at Case Western Reserve School of Medicine and University Hospitals of Cleveland that linked consumption of a high fat diet early in life to greater development later in life of Alzheimer's disease. People who have the genetic marker ApoE-E4 allele are particularly susceptible, with a seven times greater risk of developing the disease if they consumed a high fat diet than those with the genetic marker who consumed a low fat diet. In patients with the genetic marker aged sixty and older who consumed a high fat diet, there was a twelve times greater risk of developing the disease than in patients without the marker with the same dietary habits. And in 20-39 year olds, a high fat diet plus the genetic marker increased their incidence of Alzheimer's to that of twenty-three times that of those on a similar diet without the marker. The study, beginning in 1991, analyzed the diets of 232 healthy people and 72 Alzheimer's patients. Study participants were mostly in their seventies at the beginning of the study. The ApoE-E4 allele has been previously linked with Alzheimer's disease. Lead researcher Grace Petot of Case Western Reserve University School of Medicine commented, "We know that peoples' diets change with time; particularly, the intake of total fat and saturated fat seems to increase when people age from 40 to 60 years . . . What this study tells us is that we need to look a lot harder at peoples' habits, particularly since we saw an association between fat consumption at a relatively early age and the subsequent development of Alzheimer's disease." Petot noted that the control subjects consumed more antioxidants, which may have exerted a protective effect.
—D Dye
August 4, 2000
RhoC gene essential to metastasis The August 3 issue of the journal Nature published an article concerning the discovery that the RhoC gene is highly expressed in both mouse and human melanoma metastases, as compared to primary tumors. Metastasis, or the spread of a primary cancer to a distal location in the body, is the cause of most cancer deaths. Genetic expression refers to the transcription of the gene into messenger RNA. In a study of metastasized cell lines that compared 7,070 human genes and 6,347 mouse genes to the same genes in the primary tumor tissue those lines were derived from, it was found that only 16 human and a similar number of mouse genes had significantly higher expression in the metastases. Out of these, only three genes were shared by both human and mice metastases. These were the genes for fibronectin, thymosin beta 4 and RhoC. Fibronectin increases the migration of several cell types, and thymosin beta 4 may relate to the need for cells to migrate. RhoC gene is a member of the Rho family, some of which regulate cell migration. In some experiments, Rho genes were shown to contribute to cell transformation to a cancerous state. Lead study author Edwin A Clark went on to determine whether the RhoC gene was essential for metastasis. The gene was cloned and introduced by a virus into cells that had poor metastatic capability. Overexpression of the RhoC gene was shown to greatly enhance metastasis of these cells. The authors expressed surprise that this occurred with expression of only one gene.
The RhoC gene appears to be essential for metastasis. The authors are currently researching RhoC's capability of causing other tumor cells to metastasize and hope that study of the RhoC gene will lead to methods of inhibiting metastasis, the killer in cancer.
—D Dye
August 2, 2000
Soy isoflavones prevent LDL oxidation The American Journal of Clinical Nutrition, in their August issue, published the results of a study in which soy isoflavones were shown to lower oxidation of LDL cholesterol. LDL oxidation has been shown to be a factor in atherosclerosis, and therefore, heart disease. Study participants were given textured soy protein each day that contained either high levels of isoflavones, the component of soy believed to confer most of soy's benefits, or soy protein from which the isoflavones had been extracted for two periods of seventeen days, separated by a twenty-five day wash-out period. The subjects were requested not to make any changes in their exercise levels or diets during the study. Blood samples were collected from the participants and plasma isoflavone levels measured . The LDL fractions were isolated and tested for oxidation.
Those subjects who consumed the high isoflavone soy protein had predictably higher plasma isoflavone levels, as well as significantly lower markers of oxidation of LDL than did the participants who received the isoflavone-deficient soy. Subsequently, the LDL fractions were challenged with copper ions to stimulate oxidation. Samples of LDL from those having received the isoflavone-rich soy took longer to oxidize.
Soy isoflavones genistein, daidzien and equol have been shown to be antioxidants in vitro (outside the body). The isoflavone equol is made in the intestines from daidzein, and the study authors note that it "is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation." This study is significant because it measured oxidation in vivo (in the body), rather than in vitro. Since both groups received soy, it also demonstrates that it is the isoflavone component of soy that appears to be important in inhibiting oxidation of LDL.
—D Dye
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