Contact: Angela Babb
American Academy of Neurology
ST. PAUL, Minn. – People taking cholesterol-lowering drugs such as atorvastatin after a stroke may be at an increased risk of hemorrhagic stroke, or bleeding in the brain, a risk not found in patients taking statins who have never had a stroke. But researchers caution the risk must be balanced against the much larger overall benefit of the statin in reducing the total risk of a second stroke and other cardiovascular events when making treatment decisions. The research is published in the December 12, 2007, online issue of Neurology®, the medical journal of the American Academy of Neurology.
For the study, researchers conducted a secondary analysis of the results of the Stroke Prevention with Aggressive Reduction in Cholesterol Levels (SPARCL) clinical trial. The trial enrolled 4,731 people who were within one to six months of having had a stroke or transient ischemic attack, or mini-stroke, and with no history of heart disease. Half of the participants received atorvastatin and half received a placebo. The participants were then followed for an average of four and a half years.
Overall, treatment was associated with a 16-percent reduction in total stroke, the study’s primary endpoint, as well as significant reductions in coronary heart events. However, secondary analysis found that the overall reduction in stroke included an increase in the risk of brain hemorrhage. Of those people randomized to atorvastatin, the study found 2.3 percent experienced a hemorrhagic stroke during the study compared to 1.4 percent of those taking placebo. The study also found there was a 21-percent reduction in ischemic stroke, a more common type of stroke involving a block in the blood supply to the brain, among people taking atorvastatin.
Other factors were also found to increase the risk of brain hemorrhage. For example, those who had experienced a hemorrhagic stroke prior to the study were more than five times as likely to suffer a second stroke of this kind. Men were also nearly twice as likely as women to suffer a hemorrhagic stroke. People with severe high blood pressure at their last doctor’s visit prior to the hemorrhagic stroke had over six times the risk of those with normal blood pressure.
“Although treatment of patients with a stroke or transient ischemic attack was clearly associated with an overall reduction in a second stroke, hemorrhagic stroke was more frequent in people treated with atorvastatin, in those with a prior hemorrhagic stroke, in men and in those with uncontrolled hypertension,” according to study author Larry B. Goldstein, MD, with Duke University Medical Center in Durham, North Carolina, and Fellow of the American Academy of Neurology. “This risk of hemorrhagic stroke also increased with age.”
“Treatment with atorvastatin did not disproportionately increase the frequency of brain hemorrhage associated with these other factors. The risk of hemorrhage in patients who have had a transient ischemic attack or stroke must be balanced against the benefits of cholesterol-lowering drugs in reducing the overall risk of a second stroke, as well as other cardiovascular events,” said Goldstein.
The SPARCL trial was funded by Pfizer, the maker of atorvastatin.
The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson disease, and multiple sclerosis.
For more information about the American Academy of Neurology, visit http://www.aan.com.
Contact: Richard Merritt
Duke University Medical Center
DURHAM, N.C. – Long denigrated as vestigial or useless, the appendix now appears to have a reason to be – as a “safe house” for the beneficial bacteria living in the human gut.
Drawing upon a series of observations and experiments, Duke University Medical Center investigators postulate that the beneficial bacteria in the appendix that aid digestion can ride out a bout of diarrhea that completely evacuates the intestines and emerge afterwards to repopulate the gut. Their theory appears online in the Journal of Theoretical Biology.
“While there is no smoking gun, the abundance of circumstantial evidence makes a strong case for the role of the appendix as a place where the good bacteria can live safe and undisturbed until they are needed,” said William Parker, Ph.D., assistant professor of experimental surgery, who conducted the analysis in collaboration with R. Randal Bollinger, M.D., Ph.D., Duke professor emeritus in general surgery.
The appendix is a slender two- to four-inch pouch located near the juncture of the large and small intestines. While its exact function in humans has been debated by physicians, it is known that there is immune system tissue in the appendix.
The gut is populated with different microbes that help the digestive system break down the foods we eat. In return, the gut provides nourishment and safety to the bacteria. Parker now believes that the immune system cells found in the appendix are there to protect, rather than harm, the good bacteria.
For the past ten years, Parker has been studying the interplay of these bacteria in the bowels, and in the process has documented the existence in the bowel of what is known as a biofilm. This thin and delicate layer is an amalgamation of microbes, mucous and immune system molecules living together atop of the lining the intestines.
“Our studies have indicated that the immune system protects and nourishes the colonies of microbes living in the biofilm,” Parkers explained. “By protecting these good microbes, the harmful microbes have no place to locate. We have also shown that biofilms are most pronounced in the appendix and their prevalence decreases moving away from it.”
This new function of the appendix might be envisioned if conditions in the absence of modern health care and sanitation are considered, Parker said.
“Diseases causing severe diarrhea are endemic in countries without modern health and sanitation practices, which often results in the entire contents of the bowels, including the biofilms, being flushed from the body,” Parker said. He added that the appendix’s location and position is such that it is expected to be relatively difficult for anything to enter it as the contents of the bowels are emptied.
“Once the bowel contents have left the body, the good bacteria hidden away in the appendix can emerge and repopulate the lining of the intestine before more harmful bacteria can take up residence,” Parker continued. “In industrialized societies with modern medical care and sanitation practices, the maintenance of a reserve of beneficial bacteria may not be necessary. This is consistent with the observation that removing the appendix in modern societies has no discernable negative effects.”
Several decades ago, scientists suggested that people in industrialized societies might have such a high rate of appendicitis because of the so-called “hygiene hypothesis,” Parker said. This hypothesis posits that people in “hygienic” societies have higher rates of allergy and perhaps autoimmune disease because they — and hence their immune systems — have not been as challenged during everyday life by the host of parasites or other disease-causing organisms commonly found in the environment. So when these immune systems are challenged, they can over-react.
“This over-reactive immune system may lead to the inflammation associated with appendicitis and could lead to the obstruction of the intestines that causes acute appendicitis,” Parker said. “Thus, our modern health care and sanitation practices may account not only for the lack of a need for an appendix in our society, but also for much of the problems caused by the appendix in our society.”
Parker conducted a deductive study because direct examination the appendix’s function would be difficult. Other than humans, the only mammals known to have appendices are rabbits, opossums and wombats, and their appendices are markedly different than the human appendix.
Parker’s overall research into the existence and function of biofilms is supported by the National Institutes of Health. Other Duke members of the team were Andrew Barbas, Errol Bush, and Shu Lin.
Mouse experiments reveal ‘flight or fight’ hormone’s role
Contact: Nick Zagorski
Johns Hopkins Medical Institutions
Both extensive psychological research and personal experiences confirm that events that happen during heightened states of emotion such as fear, anger and joy are far more memorable than less dramatic occurrences. In a report this week in Cell, Johns Hopkins researchers and their collaborators at Cold Spring Harbor and New York University have identified the likely biological basis for this: a hormone released during emotional arousal “primes” nerve cells to remember events by increasing their chemical sensitivity at sites where nerves rewire to form new memory circuits.
Describing the brain as a big circuit board in which each new experience creates a new circuit, Hopkins neuroscience professor Richard Huganir, Ph.D. says that he and his team found that during emotional peaks, the hormone norepinephrine dramatically sensitizes synapses – the site where nerve cells make an electro-chemical connection – to enhance the sculpting of a memory into the big board.
Image showing phosphorylated GluR1 receptors congregating around sites of neuronal synapses.
Norepinephrine, more widely known as a “fight or flight” hormone, energizes the process by adding phosphate molecules to a nerve cell receptor called GluR1. The phosphates help guide the receptors to insert themselves adjacent to a synapse. “Now when the brain needs to form a memory, the nerves have plenty of available receptors to quickly adjust the strength of the connection and lock that memory into place,” Huganir says.
Huganir and his team suspected that GluR1might be a target of norepinephrine since disruptions in this receptor cause spatial memory defects in mice. They tested the idea by either injecting healthy mice with adrenaline or exposing them to fox urine, both of which increase norepinephrine levels in brain. Analyzing brain slices of the mice, the researchers saw increased phosphates on the GluR1 receptors and an increased ability of these receptors to be recruited to synapses.
When the researchers put mice in a cage, gave a mild shock, took them out of that cage and put them back in it the next day, mice who had received adrenaline or fox urine tended to “freeze” in fear – an indicator they associated the cage as the site of a shock – more frequently, suggestive of enhanced memory.
However, in a similar experiment with mice genetically engineered to have a defective GluR1 receptor that phosphates cannot attach to, adrenaline injections had no effect on mouse memory, further evidence of the “priming” effect of the receptor in response to norepinephrine.
The researchers plan on continuing their work by going in the opposite direction and engineering another mouse strain that has a permanently phosphorylated or “primed” receptor. “We’re curious to see how these mice will behave,” Huganir says. “We suspect that they’ll be pretty smart, but at the same time constantly anxious.”
The research was funded by the National Institutes of Health, Damon Runyon Postdoctoral Fellowship, NARSAD, and the Ale Davis and Maxine Harrison Foundation
Authors on the paper are Hailan Hu, Eleonore Real, and Roberto Malinow of Cold Spring Harbor Laboratory; Joe LeDoux of New York University; and Kogo Takamiya, Myoung-Goo Kang, and Huganir of Johns Hopkins
Contact: Amy Molnar
John Wiley & Sons, Inc.
A new study examined the possible associations between occupation and the risk of dying from systemic autoimmune diseases and found that occupational exposures in farming and industry may be linked to higher death rates from these diseases.
More than 8 million Americans suffer from autoimmune diseases, in which the immune system attacks the body’s own tissues and several occupational exposures have been linked to systemic autoimmune diseases, which affect multiple organs. A new study published in the October issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis) examined the possible associations between occupation and the risk of dying from systemic autoimmune diseases and found that occupational exposures in farming and industry may be linked to higher death rates from these diseases.
Led by L.S. Gold and A.J. De Roos, of the Fred Hutchinson Cancer Research Center in Seattle, WA, researchers examined death certificate data from 26 states from 1984 to 1998. Any cases that listed a systemic autoimmune disease (for example, rheumatoid arthritis) as a cause of death, were included, as were disease types with a suspected systemic autoimmune disease origin (such as unspecified connective tissue disorder). Five control subjects matched by age, sex, race, year of death and geographic region were also selected. The researchers established each person’s longest-held occupation from the “usual occupation” listed on the death certificate. In addition, they examined specific exposures based on occupation and industry. These included asbestos, solvents, benzene, pesticides and other substances. Occupations involving significant exposure to the public (such as teachers, and waiters/waitresses) or animals were also tracked.
The results showed that some occupations involving exposure to the public (such as nurses and teachers) were associated with an increased risk of dying from a systemic autoimmune disease but this was not the case with all jobs involving public exposure (for example food service jobs). Farmers showed increased risk of death from systemic autoimmune disease, particularly for those who worked with crops versus livestock. In addition, several industrial occupations such as mining and textile machine operators, as well as timber cutting and logging had an increased risk of death from this group of diseases.
Further analysis showed that the same occupations and exposures were present in those who were older than the typical retirement age when they died, “implying that the occupational exposures were involved in a chronic pathogenic process leading to either disease incidence or slow progression of existing autoimmunity,” according to the authors. They suggest that the higher risk associated with jobs involving public contact may be due to exposure to multiple infectious agents leading to an autoimmune response.
The authors note that autoimmune diseases tend to be underreported on death certificates, and that the increased risk seen with certain occupations, such as teachers, may be due to the fact that these individuals have extensive health benefits even after retirement, and therefore better access to care. This would also help explain why other occupations that involve public contact but lower health insurance coverage, such as waiter/waitress, seemed to have a lower risk of death from autoimmune disease. However, not all the occupational associations they found are expected to be affected by insurance status.
“The size of our study allowed us to estimate associations between specific occupations and death from autoimmune diseases and to generate hypotheses that will be useful as starting points for future studies in this area,” the authors conclude. They note that future studies should focus on obtaining more detailed occupational histories from the groups found to be at increased risk.
Article: “Systemic Autoimmune Disease Mortality and Occupational Exposures,” L.S. Gold, M.H. Ward, M. Dosemeci, A.J. De Roos, Arthritis & Rheumatism, October 2007; (DOI: 10.1002/art.22880).
The most accurate measures of European daily temperatures ever indicate that the length of heat waves on the continent has doubled and the frequency of extremely hot days has nearly tripled in the past century. The new data shows that many previous assessments of daily summer temperature change underestimated heat wave events in western Europe by approximately 30 percent.
Paul Della-Marta and a team of researchers at the University of Bern in Switzerland compiled evidence from 54 high-quality recording locations from Sweden to Croatia and report that heat waves last an average of 3 days now—with some lasting up to 4.5 days—compared to an average of around 1.5 days in 1880. The results are published 3 August in the Journal of Geophysical Research-Atmospheres, a publication of the American Geophysical Union. The researchers suggest that their conclusions contribute to growing evidence that western Europe’s climate has become more extreme and confirm a previously hypothesized increase in the variance of daily summer temperatures since the 19th century.
The study adds evidence that heat waves, such as the devastating 2003 event in western Europe, are a likely sign of global warming; one that perhaps began as early as the 1950s, when their study showed some of the highest trends in summer mean temperature and summer temperature variance.
“These results add more evidence to the belief among climate scientists that western Europe will experience some of the highest environmental and social impacts of climate change and continue to experience devastating hot summers like the summer of 2003 more frequently in the future,” Della-Marta said.
The authors note that temperature records were likely overestimated in the past, when thermometers were not kept in modern Stevenson screens, which are instrument shelters used to protect temperature sensors from outside influences that could alter its readings. The researchers corrected for this warm bias and other biases in the variability of daily summer temperatures and show that nearly 40 percent of the changes in the frequency of hot days are likely to be caused by increases in summer temperatures’ variability. This finding demonstrates that even a small change in the variance of daily summer temperatures can radically enhance the number of extremely hot days.
“These findings provide observational support to climate modeling studies showing that European summer temperatures are particularly sensitive to global warming,” Della-Marta said. “Due to complex reactions between the summer atmosphere and the land, the variability of summer temperatures is expected to [continue to] increase substantially by 2100.”
The research was supported by the European Environment and Sustainable Development Program, the Swiss National Science Foundation and the National Center for Excellence in Climate Research (NCCR Climate).
Contact: Jonathan Lifland
American Geophysical Union
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