Wednesday, May 20, 2009

satisfying 6.bts.003004 Louis J. Sheehan, Esquire

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Thanks to better screening, prevention and treatment, death rates from cancer in the United States have declined steadily in recent decades. But a new study finds that while college graduates have benefited from this trend, people who didn’t finish high school have lagged behind and even missed out on some of these gains.

Much of the discrepancy stems from differences between the groups in taking preventive measures such as quitting smoking or using cancer screening options, says study coauthor Ahmedin Jemal, an epidemiologist at the American Cancer Society in Atlanta.

But a lot can also be traced to the fact that 47 million people in the United States are uninsured, he says. Education levels closely track with socioeconomic levels, and that means access to good health care and insurance coverage to pay for it, he says.

Jemal and his colleagues analyzed data collected by the National Center for Health Statistics, part of the Centers for Disease Control and Prevention, from death certificates filed in 37 states and the District of Columbia. The research team concentrated on people ages 25 to 64 who had died from 1993 to 2001, calculating mortality rates during that time period for the four most common cancers—lung, colorectal, breast and prostate. The sampling of the non-Hispanic population included more than 500,000 deaths.

The researchers report in the July 16 Journal of the National Cancer Institute that while some death rates fell dramatically between these time posts, significant differences emerged across the board based on educational background. For example, the death rate from lung cancer over that span dropped by 5 percent annually in white men and 7 percent annually in black men who had been through college. But among men who had dropped out of high school, the lung cancer death rate remained largely unchanged in whites and dropped less than 1 percent a year in blacks.

Meanwhile, colorectal cancer fell significantly over that time in men and women, black and white, who had gone to college, but not in their counterparts who hadn’t finished high school.

Other research shows that roughly 50 percent or more of highly educated people get regular colonoscopies that can catch and remove colorectal cancer early, but that among poorly educated people the number is closer to 30 percent, Jemal says. “The difference by education is mind-boggling,” he says.

Among whites, breast cancer death rates declined broadly, and women with more education showed greater decreases. But among black women, only those with four years of college showed clear declines.

In men, prostate cancer deaths showed a strong education-related decline among white men, but less of a decline for black men.

Much of the effect seen in this study could reflect access to health care, says health economist Cathy Bradley of Virginia Commonwealth University in Richmond. But another factor could play an equally important role, she says.

“I think education is a marker for something else,” she says. “People who invest in an education also invest in their health and place a higher value on the future than on the present.” Hypothetically, this prioritizing would be reflected in lifestyle, and these people might even seek out jobs with better insurance plans.

In contrast, people who don’t invest in the future, as in a high school diploma or a college degree, may place more value on the present, she says. Because cancer is an invisible disease whose causes have little immediate impact, these people may concentrate on satisfying immediate needs and show less regard for future risks. Louis J. Sheehan, Esquire

Monday, May 4, 2009

neorons 4.neu.0001 Louis J. Sheehan, Esquire

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Most of the brain does fine with its original brain cells, but parts involved in smelling and remembering sometimes need some new recruits.

In mice, new neurons are needed to remember mazes and keep their scent-sensing organs plump (but aren’t necessary for detecting smells), a new study shows. Another recent study demonstrates that some antidepressants require neurogenesis — the creation of fresh neurons — to work.

Both studies are part of a new wave of research that shows neurogenesis — once thought to be impossible in the brain — plays an important role in the organ’s function.

“These are both very good papers and consistent with the growing appreciation for the importance of adult neurogenesis in general and in particular in behavior,” says Fred “Rusty” Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, Calif.

Neurogenesis creates new neurons in the hippocampus, a part of the brain linked to learning and memory, and in the olfactory bulb, an organ that detects smells and pheromones. But scientists didn’t know why it was necessary to make new cells in those brain regions.

Japanese researchers led by Ryoichiro Kageyama, a neuroscientist at Kyoto University, report August 31 in an advance online publication of Nature Neuroscience that neurogenesis plays different roles in the two brain structures.

Nearly all of the cells in the olfactory bulb are replaced, and that refreshing of neurons is required to maintain the shape and volume of the bulb, the researchers report. But mice with shrunken olfactory bulbs had no trouble sniffing out sweet treats, suggesting that a few old neurons are all that’s needed to maintain a sense of smell.

Neural stem cells that make new olfactory bulb neurons seem to act like the adult stem cells that maintain skin, blood and gut, says Kageyama. But the researchers don’t yet understand why a breakdown in maintenance doesn’t destroy the mice’s sense of smell.

“Smell is so important for mice that redundancy in olfaction could be intensive,” Kageyama says. “It is also possible that the mice have some olfactory defect that we are so far not aware of.” The team has not yet tested whether mice with atrophied olfactory bulbs can still detect pheromones.

In contrast to the olfactory bulb, far fewer new neurons are added to the hippocampus. More than 10 percent of neurons are replaced in the hippocampus, but their addition doesn’t make the brain region bigger, and blocking neurogenesis doesn’t make the hippocampus shrink, Kageyama and his colleagues found. There might be only a few new neurons, but they are important for mice to form memories, the researchers say. Blocking neurogenesis impaired mice’s ability to remember a maze for more than week, while mice with intact hippocampuses remembered the maze two weeks after learning to run it.

“It’s not a straightforward linkage between neurogenesis and memory,” says Paul Frankland, a neuroscientist at the Hospital for Sick Children Research Institute in Toronto, who was not involved in the new studies.Memories can still form in the absence of neurogenesis, but may be subtly different from those made when new neurons are present, he says. Neurogenesis may help form a timeline for memories, with new neurons helping to keep track of memories formed at the time the cells joined the hippocampus.

Neurogenesis in the hippocampus slows down as mice age. Similar slowing in people could help explain why memory fails as people get older, Kageyama says.

Another mystery about neurogenesis concerns antidepressants known as selective serotonin reuptake inhibitors or SSRIs, the class of drug that includes Prozac. Those drugs were previously shown to stimulate neurogenesis in the hippocampus, but scientists were not sure if that was a side effect of the medication or necessary for its action.

Now, a study on mice in the Aug. 14 Neuron shows that neurogenesis in the hippocampus depends on the action of a protein called TRKB, and that neurogenesis is required for the antidepressant effects of SSRIs.

That doesn’t mean that depression is caused by a defect in neurogenesis, says Luis Parada, who led the study with colleagues at the University of Texas Southwestern Medical Center at Dallas. But the research could shed light on why some people don’t respond to antidepressant therapy and lead to the development of new drugs to treat depression.

“There is exciting evidence that in a variety of animal models neurogenesis accompanies response to antidepressants,” he says. “We’re getting an idea of what molecules mediate this.”

Friday, May 1, 2009

architecture 7.arc.0098 Louis J. Sheehan, Esquire

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When it comes to sensory information detected by the body, pain is king, and itch is the court jester. But that insistent, tingly feeling—satisfied only by a scratch—is anything but funny to the millions of people who suffer from it chronically.

Garden-variety itches related to histamine, like the kind caused by an angry rash of chicken pox or poison ivy, annoy everyone, but most can be subdued with drugs like Benadryl. But another type of itch is not mollified by these drugs, and therein lies the rub. Pathological itch — called the “itch that laughs at Benadryl” by neuroscientist and itch investigator Glenn Giesler Jr. of the University of Minnesota—is no joke.

Not often pursued by scientists who look at sensation, itch research has lagged far behind investigations of other bodily cues. But in recent years, scientists have begun studying pathological itch seriously. This year researchers found nerve fibers—long, thin strands that carry information from the outer skin to the spinal cord and ultimately, the brain—built to detect this often-devastating type of itch. The new results show that it has its own pathway to the brain.

“That’s the hottest topic in the field right now, the idea of different pathways for different itches,” says Earl Carstens, a neurobiologist at the University of California, Davis who studies the details of how these itches travel to the brain. The discovery of these fibers has also led some researchers to rethink the relationship between pain and itch.

“In the last two years, there has been an exponential growth of publications in the field, with major findings,” says Gil Yosipovitch, a researcher and clinician at Wake Forest University in Winston-Salem, N.C., who founded the International Forum for the Study of Itch in 2005.

Increasing attention to itch is good news for the estimated 17 million Americans with severe, chronic itch from atopic eczema, a skin disease marked by dry, itchy skin, and other itchy conditions. A large study on itch conducted in Oslo in 2004 found that 8 percent of more than 18,000 adult Norwegians surveyed suffered from chronic itch. Itch often afflicts the weakest: It is a well-known but understudied symptom in people with liver failure, multiple sclerosis, HIV and late-stage cancer. Painkillers may help the seriously ill, but often replace pain with severe itchiness. http://LOUIS-J-SHEEHAN.INFO And depression rates soar among people who itch constantly.

It’s easy to imagine why. Think of spiny insect legs scurrying up the neck, and of lice, mosquitoes, bedbugs and chiggers crawling on, burrowing in and biting tender parts of the skin. Now magnify those sensations by months, years or even decades.

For patients and doctors, the worst part of this itch is that there is almost no way to treat it. Antihistamines like Benadryl, the tried-and-true way of blocking itch caused by bug bites and hives, have no effect on more serious itch conditions. In many cases, the best (and only) advice has remained unchanged for many years: Moisturize, wear loose clothing and, whatever you do, don’t scratch.

“It’s maddening,” says Susan Lipworth, a board member of the National Eczema Association, based in San Rafael, Calif., who has suffered from severe eczema-related itching for 14 years. The insatiable desire to scratch has left her body scarred with seeping wounds. “I love my doctors, but there is nothing for this,” she says.

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Enlargemagnify
NEVER-ENDING ITCHENLARGE Pathological itch, unlike garden-variety itch, cannot be subdued with drugs like Benadryl. Amy Guip

The original itching

Plants and bugs can make us itch. So can scratchy wool sweaters. It turns out that itch can even be brought on by the power of suggestion.

You feel an itch on the skin. But its roots lie deep in the brain and spinal cord, a finding that emerged from scientists’ first modern attempts to understand itch in the 1970s and 1980s. Studying the itches brought on by things like poison ivy, scientists showed that after contact with the plant’s toxins, the skin releases a chemical called histamine from specialized cells that cause the skin to swell, redden and itch.

Early work by European researchers showed that histamine causes intense itch when injected directly into human skin. It wasn’t until 1997 that a German research group led by Martin Schmelz, now at the University of Heidelberg in Mannheim, discovered the first itch nerve fibers, which responded primarily to histamine and were shown not to be sensitive to pain (SN: 10/18/97, p. 245).

“The idea was fabulous,” says Robert LaMotte, a neurobiologist at Yale University and a leader of studies on the newly discovered chronic itch fibers.

Until the 1997 finding, most researchers thought that itch was a weaker form of pain, and probably sensed by pain-related nerves. Scientists believed that if an itchy stimulus was increased to a high enough level, the itch would turn into an “ouch.” Conversely, if a painful poke was lessened enough, the pain would feel itchy. But the discovery of fibers that responded to histamine but not to a painful pinch revealed itch as a sensation unto itself.

“The idea that histamine is the main itch mediator in the skin was prevalent for a long time,” Carstens says.

The study of histamine itch led to major gains in understanding a chemical that causes itch and the fibers that detect it, but in a sense, it was a red herring. Even then scientists knew that some itching didn’t appear to involve histamine.

Laughing at Benadryl
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Enlargemagnify
ITCHY PATHWAYSENLARGE Researchers have identified two distinct types of nerve fibers that respond to itchy sensations, passing signals from the skin to the brain. View the diagram for more details.Charles Floyd

“It all started with the observations of itch that are resistant to antihistamines. That’s why we embarked on this research,” says Matthias Ringkamp, a neurobiologist at Johns Hopkins University in Baltimore who has worked with LaMotte on the chronic types of itch.

Another clue also led scientists to look for separate pathways for these types of itch: The nerve endings discovered by Schmelz’s group in 1997 cannot detect many types of itch, like the kind caused by unlined prickly wool pants raking against dry winter legs. Researchers thought it might be possible to use temporary nonhistamine itches as experimental proxies for chronic, debilitating itches.

To study the itches in the lab, scientists turned to cowhage, a major ingredient in pranksters’ itching powder. Back in the 1950s, scientists had described the curiously itchy effects of cowhage, or Mucuna pruriens, a tropical plant with white or purple flowers that produces nutritious beans. Its seedpods are coated with tiny lances called spicules. When lodged in the skin, the spicules produce an intense, pure and reproducible itch that lasts for about six minutes. (Probably a very long six minutes for the study participants.)

“You can take Benadryl all day, and if you jump into a cowhage plant, you’ll itch like no tomorrow,” says Giesler, whose University of Minnesota research group was, in 2004, one of the first since the 1950s to take advantage of cowhage’s itchiness. “Right away, we realized that cowhage was a different type of itch.”

To draw distinctions between itches, a team of researchers led by Ringkamp conducted experiments using histamine for the usual itch and using cowhage to represent chronic itch. Although the study subjects found both substances to be itchy, the characteristics of the itches were markedly distinct. The itchy area caused by cowhage was restricted to the site of application; the histamine itch spread out from the original site. When an antihistamine was applied to the itches, the cowhage itch persisted.

But when Ringkamp and colleagues treated the itches with the compound that makes chili peppers hot —capsaicin, which triggers a pain response — they blocked the cowhage itch, while leaving the histamine itch unaffected. There was another notable difference. The cowhage itch disappeared in about six minutes, while the histamine itch lasted longer.

These results, published in 2007 in the Journal of Neuroscience, showed that while the sensation of the two itches caused by histamine and cowhage felt similar to participants, the mechanisms were undoubtedly different.

Since, like almost all types of chronic, pathological itches, the itch produced by cowhage is impervious to antihistamines, scientists reasoned that if they could figure out exactly which neural fibers were responsible for a cowhage itch, they might understand how pathological itch works. Then, they could figure out how to treat it. The scientists concluded that different itch fibers may carry distinct itch messages to the brain.

Because the histamine-sensing itch fibers could not detect itchy mechanical stimuli, like a scratchy wool sweater, the researchers turned to another likely culprit: pain fibers.

Pain and the itch

Called an “exquisite pleasure” by researcher G.H. Bishop in 1948, scratching an itch is deeply satisfying, probably because the pain caused by scratching overrides itch fiber activity. But the relationship between pain and itch is, to put it mildly, complicated.

After the 1997 discovery of the itch-specific fibers, itch and pain were uncoupled. The new data on cowhage-induced itch suggests that pain and itch, in some cases, do seem to be linked, and perhaps detected by the very same fibers. The finding makes the idea of a clean separation a bit fuzzier.

To see the activity of individual fibers that might respond to pain and itch, LaMotte’s team began eavesdropping on the neurons of monkeys. The researchers wanted to know if a type of nerve fiber that detects pain caused by heat and mechanical forces, such as a pinch, could also sense a cowhage-induced itch.

To test this idea, thin, conductive wires were inserted into the skin of a sedated monkey, and different types of stimuli were applied to the arm: Heat and capsaicin to cause pain, and cowhage and histamine to bring on the itch.

The team tapped into individual nerve endings as they responded to pain. A few showed a weak response when histamine was applied. But the majority of the nerve fibers responded strongly to cowhage. The same fibers known to detect painful stimuli like a hard poke or a burn could also detect the cowhage itch. These fibers were pulling double duty.

Vocabulary for itch fibers is lacking, so Ringkamp’s group described these new itch fibers, in the July 23 Journal of Neuroscience, by their pain fiber names.

Cowhage itch has a private pathway to the brain, independent of the histamine-related pathway, and scientists assume chronic itch conditions do too, Carstens says. “The idea is that there are now at least two separate mechanisms and pathways for itch, one for histamine and another one for cowhage,” he says.

Ringkamp explains: “These two kinds of itch induce two different types of neuronal populations.”

Louis J. Sheehan, Esquire And then there’s the contagious itch, similar to the yawn that can overtake a room. In a 2000 study titled “Observations during an Itch-Inducing Lecture,” viewing slide shows starring fleas, mites and allergic rashes led people to scratch themselves.

Even reading about itches may be enough to cause the sensation. (Sorry for the scratch marks.)

Understanding the architecture of the types of nerve fibers that detect itch and the complicated brain processing that makes a person want to scratch, scientists say, will lead to a greater understanding of how bodies perceive these sensations. As LaMotte, the neurobiologist from Yale, puts it, “This is a window into how the brain processes stimuli.” Louis J. Sheehan, Esquire

Despite all this progress, most researchers in the field agree that the task of classifying and describing all of the different sensory fibers in skin is in its infancy. Scientists, they say, have just scratched the surface.