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December 27, 2005
Mechanisms Of Cancer Generation
"We're not contradicting the view that genetic changes occur in the development of cancers, but there also are epigenetic changes and those come first," says lead author Andrew Feinberg, M.D., M.P.H., King Fahd Professor of Medicine and director of the Center for Epigenetics in Common Human Disease at Johns Hopkins.
Cells affected by epigenetic changes look normal under a microscope at low levels of resolution, Feinberg says, "but if you look carefully at the genome, you find there are subtle changes." By tracking these changes, he suggests, doctors potentially could treat people before tumors develop in much the same way as cardiologists prescribe cholesterol-lowering drugs to help prevent heart disease.
Epigenetic changes -- those that don't affect the gene's sequence of DNA but change the gene in other ways -- influence a wide variety of human diseases, including cancer, birth defects and psychiatric conditions. Epigenetic alterations include the turning off or quieting of genes that normally suppress cancer and the turning on of oncogenes to produce proteins that set off cancerous behavior.
Epigenetic changes are found in normal cells of patients with cancer and are associated with cancer risk, Feinberg notes.
As one example, as per a research findings published in the Feb. 24, 2005, online version of Science, Feinberg and his colleagues in the United States, Sweden and Japan reported that mice engineered to have a double dose of insulin-like growth factor 2 (IGF2) had more primitive precursor cells in the lining of the colon than normal mice. When these mice also carried a colon-cancer-causing genetic mutation, they developed twice as a number of tumors as mice with normal IGF2 levels. The extra IGF2 stemmed not from a genetic problem, or mutation, but from an epigenetic problem that improperly turned on the copy of the IGF2 gene that should have remained off.........
December 27, 2005
Blocking The Nerve Receptor Reduces Brain Damage
The finding holds promise for the development of effective alternatives to anti-inflammatory drugs called COX inhibitors, which have potentially lethal side effects that limit their use, says Sylvain Dore, Ph.D., an associate professor in the departments of Anesthesiology and Critical Care Medicine and Neuroscience at The Johns Hopkins University School of Medicine. Dore is senior author of the paper, published in the recent issue of Toxicological Sciences. "Our work has shifted the focus from drugs that inhibit COX-2 to drugs that block the EP1 receptor," Dore said.
Receptors are protein-docking sites on cells into which "signaling" molecules such as nerve chemicals or hormones insert themselves. This binding activates the receptor, which transfers the signal into the cell to produce a specific response.
COX inhibitors block the ability of the enzyme cyclooxygenase-2 (COX-2) to make prostaglandin E2 (PGE2), a hormonelike substance long linked to inflammation and other effects. The Hopkins study results suggest that PGE2 causes brain damage following stroke by binding to the EP1 receptor on nerve cells. Therefore, blocking PGE2 activity directly rather than inhibiting COX-2 could reduce brain damage in individuals who have a stroke while avoiding the side effects of COX-2 inhibitors, the Hopkins researchers say.
Prior work by others had shown that certain events, such as cerebral ischemia (stroke) and seizures, that interrupt oxygen flow to the brain also cause excessive activation of so-called NMDA receptors by the nerve chemical glutamate. Other work had suggested that activation of NMDA receptors by glutamate causes an increase in the production of COX-2, which then produces PGE2.........
December 27, 2005
Breast Cancer Numbers Increase Among New Zealand Women
Evans Bay New ZealandThe number of women in the upper South Island diagnosed with breast cancer is soaring as access to screening services improves.
Pressure is now on therapy providers who are faced with an influx of newly diagnosed cancer patients seeking radiotherapy or chemotherapy.
Mammographies provided by BreastScreen South led to 244 women in Canterbury, Nelson, Marlborough and the West Coast being diagnosed with breast cancer in the year to November. That figure compares with 159 the prior year and 143 the year before that.
A Canterbury District Health Board manager says the extra costs of treating the women with chemotherapy have added to a $2.48 million budget overrun in Christchurch Hospital's medical and surgical services division this financial year.
The age range for Government- funded breast cancer screening was extended in July last year to include all women aged 45 to 69.
However, a lack of staff and equipment meant women in the younger age bracket have only recently been able to access the programme.
Breast cancer is the leading cause of cancer deaths among New Zealand women. About 2200 women develop the disease each year and 640 die from it.
BreastScreen South clinical director Richard Chisholm said the higher number of diagnoses showed the screening extension had been a success. "It's a predictable increase, but over all we're pleased that we're detecting breast cancers".
He said some of the extra women would have been picked up anyway through private screening or by going to their GP after finding a lump.........
December 26, 2005
Arthritis Drug Effective for Depression
High concentrations of pro-inflammatory substances called cytokines, such as tumor necrosis factor-alpha (TNF-alpha), have been associated with major depression. According to Ranga Krishnan, M.D., the study author based at Duke, scientists have long hypothesized that reducing the effects of the cytokines may reverse depressive symptoms. Until now, no research team has examined the effects of a tumor necrosis factor receptor on depression in humans.
The phase III clinical trial was primarily designed to test the effectiveness of etanercept in improving the clinical symptoms of psoriasis, a chronic skin disease characterized by silvery, scaling bumps and raised patches of very dry skin. In severe cases, people can experience joint pain similar to that of rheumatoid arthritis. Psoriasis sufferers frequently experience problems with both depression and fatigue as a result of their disease.
"It has been shown that when you are sick or depressed, tumor necrosis factor concentration increases," said Krishnan, chief of psychiatry and behavioral sciences at Duke. "When TNF-alpha goes up, the symptoms are very similar to what is termed 'sickness behavior' and prior studies have shown that when a person is depressed, TNF-alpha levels are increased in blood".........
December 26, 2005
Antidepressants Boost Brain Growth
The study on rats, led by Vassilis E. Koliatsos, M.D., a neuropathologist at the Johns Hopkins University School of Medicine, found that selective serotonin reuptake inhibitors (SSRIs) increase the density of nerve-impulse-carrying axons in the frontal and parietal lobes of the neocortex and part of the limbic brain which control the sense of smell, emotions, motivation, and organs that work reflexively such as the heart, intestines and stomach. "It appears that SSRI antidepressants rewire areas of the brain that are important for thinking and feeling, as well as operating the autonomic nervous system," said Koliatsos.
Axons are long, filament-shaped extensions of neurons that, together with myelin, are the main constituents of nerves. Axons conduct chemically driven nerve impulses away from the cell body toward a narrow gap known as a synapse. Among the chemicals involved are such monoamines as norepinephrine and serotonin, which, at the synapse, are transferred to another neuron.
Antidepressants, such as Prozac, Zoloft and Paxil, have long been thought to exert their clinical effects by increasing synaptic concentrations of serotonin and norepinephrine, enhancing or stimulating their transference.
"But our findings -- that serotonin reuptake modulators increase the density of nerve synapses, particularly in the front part of the brain - may offer a better explanation of why antidepressants are effective and why they take time to work," according to Koliatsos.
For example, antidepressants increase synaptic monoamines within hours, and the regulatory effects on receptors are complete within a few days, yet clinically meaningful results from antidepressants commonly require a two- to four-week delay.........
December 26, 2005
Traditional Risk-factor Scoring And Women
"Our best means of preventing coronary heart disease is to identify those most likely to develop the condition, and intervene with changes in lifestyle and drug therapy before symptoms start to appear," says the senior author of both studies, cardiologist Roger Blumenthal, M.D., an associate professor and director of the Ciccarone Preventive Cardiology Center at The Johns Hopkins University School of Medicine and its Heart Institute. "The goal is to strongly consider therapies, such as aspirin, cholesterol-lowering medications and, possibly, blood pressure medications for individuals at higher risk, so that heart attacks will be less likely to occur in the future".
The Hopkins findings, the latest of which appear in the American Heart Journal online Dec. 16, is believed to be one of the first critical assessments of the Framingham Risk Estimate (FRE) as the principal test for early detection of heart disease. The scientists wanted to determine why a number of of these women at risk for heart disease are not identified earlier.
The FRE is a total estimate of how likely a person is to suffer a fatal or nonfatal heart attack within 10 years, and it is based on a summary estimate of major risk factors for coronary heart disease, such as age, blood pressure, blood cholesterol levels and smoking.
However, Blumenthal says, a number of women with cardiovascular problems go undetected despite use of the Framingham score. While the death rate for men from cardiovascular disease has steadily declined over the last 20 years, the rate has remained relatively the same for women, he says.........
December 26, 2005
Age Is The Major Factor inAssisted Reproduction
CDC's ninth annual ART report summarizes national trends and provides information on success rates for 399 fertility clinics around the country. Overall, 28 percent of ART procedures resulted in the birth of a baby for women who used their own fresh eggs.
The 2003 report offers more evidence that a woman's age is one of the most important factors in determining whether she will have a live birth by using her own eggs. "Women in their 20s and early 30s had relatively high rates of success for pregnancies, live births, and single live births," said Victoria Wright, a public health analyst in CDC's Division of Reproductive Health. "But success rates declined steadily once a woman reached her mid-30s."
Overall, 37 percent of the fresh non-donor procedures started in 2003 among women younger than 35 resulted in live births. This percentage of live births decreased to 30 percent among women aged 35-37, 20 percent among women aged 38-40, 11 percent among women aged 41-42 and 4 percent among women older than 42.
Women 40 or older are more likely to have a successful ART procedure if they use donor eggs. Egg donors are typically in their 20s or 30s. The average live birth rate for women who used ART with donor eggs is 50 percent, and is independent of age.
About 35 percent of ART deliveries among women who used their own fresh eggs were multiple births (twins or more), compared with 3 percent in the general U.S. population during the same time period. This is because multiple embryos are often transferred to increase the likelihood of a live birth. Multiple births are associated with greater risk for both mothers and babies, such as cesarean section, low birth weight, premature birth, and infant disability or death.........
December 26, 2005
March of Dimes New Year's Resolutions for a Healthy Baby
December 26, 2005
Evolution Research Cited
3-spine sticklebackWhen the editors at Science looked back over the research reported in 2005, they decided that several high-impact discoveries made evolution stand out as the Breakthrough of the Year. Among the research highlighted is work by David Kingsley, PhD, professor of developmental biology at Stanford University School of Medicine, who studies the evolutionary process in a diverse group of fish called the stickleback.
In a roundup of breakthroughs would be published in the journal's Dec. 23 issue, Science points out that evolution is the underpinning of all biological research. "Today evolution is the foundation of all biology, so basic and all-pervasive that researchers sometimes take its importance for granted," the editors wrote.
Kingsley's highlighted work was published in the March 25 issue of Science, when he reported finding that 15 isolated freshwater stickleback populations all lost their bony armor through mutations in the same gene. This was among the first times that researchers had shown the same genetic change was responsible for an evolutionary adaptation in disparate populations.
"Our work shows that even major morphological changes are controlled by relatively simple mechanisms," Kingsley said.
A number of scientists have previously shown evolution in biochemical processes, such as antibiotic resistance. But some evolution critics had argued that it would be impossible to evolve large morphological changes in natural populations. "That is obviously false," said Kingsley, who is also a Howard Hughes Medical Institute investigator. "Sticklebacks with major changes in skeletal armor and fin structures are thriving in natural environments. And the major differences between forms can now be traced to particular genes".
Sticklebacks evolved from a relatively uniform marine population into today's broad spectrum of shapes and sizes when the last Ice Age ended roughly 10,000 years ago. Because ocean fish quickly evolved into such distinct populations when they colonized new freshwater lakes and streams, they are an ideal model for understanding how animals adapt to their unique environments.........
December 26, 2005
Minority Patients And Children And Latest Asthma Technologies
In order to track the adoption of inhaled steroid medications for asthma after their introduction in the 1980s, the scientists analyzed data from the National Ambulatory Medical Care Survey from 1989 to 1998. In this annual survey, conducted by the National Center for Health Statistics, physicians complete a form after outpatient visits during a randomly selected week, answering questions about patients' diagnoses and the therapys provided. The scientists identified 3,671 doctor visits by patients with asthma during the years studied, determined whether or not inhaled steroids were prescribed or administered during those visits, and also analyzed information on patients' age and race or ethnicity.........
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