Gait may be associated with orgasmic ability

Paisley, Scotland – 05 sept 2008 - A new study found that trained sexologists could infer a woman's history of vaginal orgasm by observing the way she walks. The study is published in the September 2008 issue of The Journal of Sexual Medicine, the official journal of the International Society for Sexual Medicine and the International Society for the Study of Women's Sexual Health.
Led by Stuart Brody of the University of the West of Scotland in collaboration with colleagues in Belgium, the study involved 16 female Belgian university students. Subjects completed a questionnaire on their sexual behavior and were then videotaped from a distance while walking in a public place. The videotapes were rated by two professors of sexology and two research assistants trained in the functional-sexological approach to sexology, who were not aware of the women's orgasmic history.
The results showed that the appropriately trained sexologists were able to correctly infer vaginal orgasm through watching the way the women walked over 80 percent of the time. Further analysis revealed that the sum of stride length and vertebral rotation was greater for the vaginally orgasmic women. "This could reflect the free, unblocked energetic flow from the legs through the pelvis to the spine," the authors note.
There are several plausible explanations for the results shown by this study. One possibility is that a woman's anatomical features may predispose her to greater or lesser tendency to experience vaginal orgasm. According to Brody, "Blocked pelvic muscles, which might be associated with psychosexual impairments, could both impair vaginal orgasmic response and gait." In addition, vaginally orgasmic women may feel more confident about their sexuality, which might be reflected in their gait. "Such confidence might also be related to the relationship(s) that a woman has had, given the finding that specifically penile-vaginal orgasm is associated with indices of better relationship quality," the authors state. Research has linked vaginal orgasm to better mental health.
The study provides some support for assumptions of a link between muscle blocks and sexual function, according to the authors. They conclude that it may lend credibility to the idea of incorporating training in movement, breathing and muscle patterns into the treatment of sexual dysfunction.
"Women with orgasmic dysfunction should be treated in a multi-disciplinary manner" says Irwin Goldstein, Editor-in-Chief of The Journal of Sexual Medicine."Although small, this study highlights the potential for multiple therapies such as expressive arts therapy incorporating movement and physical therapy focusing on the pelvic floor."
###
This study is published in the September 2008 issue of The Journal of Sexual Medicine. Media wishing to receive a PDF copy may contact medicalnews@bos.blackwellpublishing.net.
Stuart Brody, Ph.D., is a professor in the Division of Psychology, School of Social Sciences at the University of the West of Scotland. He can be reached for questions at stuartbrody@hotmail.com.
Irwin Goldstein, MD is Director of Sexual Medicine, Alvarado Hospital San Diego and Clinical Professor of Surgery at University of California San Diego. He can be reached at San Diego Sexual Medicine 619-265-8865.
Article: "A Woman's History of Vaginal Orgasm is Discernible from Her Walk," Aurelie Nicholas, Stuart Brody, Pascal De Sutter, François de Carufel, Journal of Sexual Medicine, September 2008.
The Journal of Sexual Medicine is a peer-reviewed publication founded in 2004 and is the official journal of the International Society for Sexual Medicine, its five regional affiliated societies and the International Society for the Study of Women's Sexual Health. It publishes multi-disciplinary basic science and clinical research to define and understand the scientific basis of male and female sexual function and dysfunction. The Journal carries an Impact Factor of 6.199 and is ranked by the Thomson ISI Journal Citation Reports as the #1 urology publication in the Urology/Nephrology category worldwide. For more info, please visit www.jsm.issm.info.
The International Society for Sexual Medicine (ISSM) was founded in 1982 for the purpose of promoting, throughout the international scientific community, research and knowledge in sexual medicine, considered as the subspecialty area of medicine that embraces the study, diagnosis and treatment of the sexual health concerns of men and women. The society has over 2700 members worldwide, with five regional societies that are affiliated with ISSM: the Africa Gulf Society for Sexual Medicine, Asia Pacific Society for Sexual Medicine, European Society for Sexual Medicine, Latin American Society for Sexual Medicine, and Sexual Medicine Society of North America. For more information please visit www.issm.info.

Hallucinations in the flash of an eye

Specific brain regions show increased activity during hallucinations

Milan, Italy, 05 sept 2008– Ever seen or heard something that wasn't there? For most of us such experiences - termed hallucinations - are a normal, fleeting, brain glitch; yet for a few they are persistent, distressing and associated with a range of psychiatric, neurological and eye conditions.
In the September Issue of Cortex (http://www.sciencedirect.com/science/journal/00109452) Dominic H. ffytche at the Institute of Psychiatry in London reviews what we do know and moves the field forward, by introducing a new experimental approach to studying hallucinations as they occur.
Surprisingly little is known about brain changes that occur during hallucinations because of their brief, unpredictable nature. One cannot anticipate when a hallucination will occur, so the chances of capturing one during a brain scanning experiment are small. It has long been recognized that flashes of light at particular frequencies produce hallucinations of intricate patterns and vivid colours. Using a combination of brain imaging methods in normal subjects, the author harnesses the technique to examine localized changes in brain activity and changes in brain connections during hallucinations.
"We observed increases in activity in visual brain regions", says ffytche, "Increases in visual connection strength and an alteration in relationship between visual relay and receiving stations, together suggesting that hallucinations were caused by a transient form of 'blindness'".
The work highlights the need to consider the hallucinating brain from a wider perspective than previously thought. Changes in both localized brain activity and in connections between brain areas occur during hallucinations, raising further questions as to how these changes interact with pre-existing abnormalities in patients susceptible to hallucinations.
###
Notes to Editors:
The article is "The Hodology of Hallucinations" by Dominic H. ffytche, and it appears in Cortex, Volume 44, Issue 8 (September 2008), pp 637-648, published by Elsevier in Italy. Full text of the article featured above is available upon request. Contact v.brancolini@elsevier.com to obtain a copy. To schedule an interview, contact Dr. Dominic H. ffytche, d.ffytche@iop.kcl.ac.uk.

Loneliness undermines health as well as mental well-being

But people don't have to spend their lives being lonely

04 sept 2008--Feeling connected to others is vital to a person's mental well-being, as well as physical health, research at the University of Chicago shows.
The studies, reported in a new book, Loneliness: Human Nature and the Need for Social Connection, show that a sense of rejection or isolation disrupts not only abilities, will power and perseverance, but also key cellular processes deep within the human body.
The findings suggest that chronic loneliness belongs among health risk factors such as smoking, obesity or lack of exercise, according to lead author John Cacioppo, the Tiffany & Margaret Blake Distinguished Service Professor in Psychology at the University.
"Loneliness not only alters behavior, but loneliness is related to greater resistance to blood flow through your cardiovascular system," Cacioppo said.
"Loneliness leads to higher rises in morning levels of the stress hormone cortisol, altered gene expression in immune cells, poorer immune function, higher blood pressure and an increased level of depression.
Loneliness also is related to difficulty getting a deep sleep and a faster progression of Alzheimer's disease, said Cacioppo. He drew on recent research in preparing the book, written with William Patrick, the former science editor at Harvard University Press. The book was just published by W.W. Norton.
One of the founders of a new discipline called social neuroscience, Cacioppo used functional Magnetic Resonance Imaging (fMRI) brain scans and advanced scientific techniques to document the roles of loneliness and social connection as central regulatory mechanisms in human physiology and behavior.
The authors traced the need for connection to its evolutionary roots. In order to survive, humans needed to bond to rear their children. In order to flourish, they needed to extend their altruistic and cooperative impulses beyond narrow self-interest and immediate kin. But in the environment of evolutionary adaptation, the only real safety was in numbers.
Just as physical pain is a prompt to change behavior (such as moving a finger away from the fire), loneliness evolved as a prompt to action, signaling an ancestral need to repair the social bonds. Feelings of loneliness take a variety of forms, Cacioppo said.
"There are three core dimensions to feeling lonely—intimate isolation, which comes from not having anyone in your life you feel affirms who you are; relational isolation, which comes from not having face-to-face contacts that are rewarding; and collective isolation, which comes from not feeling that you're part of a group or collective beyond individual existence," he said.
It is not solitude or physical isolation itself, but rather the subjective sense of isolation that Cacioppo's work shows to be so profoundly disruptive. Yet, outward circumstances such as moving to a new community or losing an intimate partner can trigger loneliness.
And as the authors make clear, today's culture is not always conducive to promoting strong social bonds.
The problem of social isolation will likely grow as conventional societal structures fade. The average household size is decreasing, and by 2010, 31 million Americans—roughly 10 percent of the population—will live alone. Sociologists also have found that people report significantly fewer close friends and confidants than those a generation ago.
Cacioppo and Patrick also demonstrate how loneliness creates a feedback loop that reinforces social anxiety, fear and other negative feelings. By learning more about what underlies this experience, then learning to reframe their response, lonely individuals can reverse the feedback loop, overcome fear and find ways to reconnect.
"We try to offer some help for those who've become stuck," said Patrick. "The process begins in rediscovering those positive, physiological sensations that come during the simplest moments of human contact. But that means overcoming the fear and reaching out."
"Lonely people feel a hunger," Cacioppo added. "The key is to realize that the solution lies not in being fed, but in cooking for and enjoying a meal with others."

Statin reduces risk of repeat stroke in elderly

04 sept 2008--Age should not preclude people who have suffered a stroke or TIA (transient ischemic attack) from being treated with a "statin" drug to lower the risk of a recurrence, US and European investigators report.
According to their study in the medical journal Neurology, the risk-benefit balance is as favorable among patients over the age of 64 as it is among younger patients.
A TIA is often called a mini-stroke. However, while the symptoms eventually go away, they can be quiet disabling, and a TIA is often portends a full-blown stroke.
Statins are widely-used cholesterol-lowering drugs. In this case, researchers examined the effect of Lipitor (atorvastatin) versus an inactive placebo in about 4700 patients who'd had a recent stroke or TIA. About half the patients were age 65 or older and the others were younger.
Dr. Seemant Chaturvedi, at Wayne State University in Detroit, and his colleagues found that atorvastatin reduced the risk of having a fatal or nonfatal stroke by 10 percent in the older group and by 26 percent in the younger group.
Absolute risk reductions were 1.5 percent and 2.6 percent, respectively.
The differences between the age groups were not significant from a statistical standpoint.
All-cause mortality, reductions in LDL ("bad") cholesterol levels, treatment compliance, and rates of adverse events related to the study drug did not differ between older and younger subjects.
"In our study," Dr. Chaturvedi's group writes, "we found that elderly patients were able to maintain LDL reductions with atorvastatin with a low rate of serious side effects." Therefore, they should be encouraged stick with treatment for the long term.
SOURCE: Neurology, online September 3, 2008.

New breast cancer screening tool shows promise

By Will Dunham
04 sept 2008--A new screening tool works three times better than mammography at finding tumors in women who have dense breast tissue, which can confound mammograms, U.S. researchers said on Wednesday.
Mammography, an X-ray of the breasts, detected fewer than a third of the tumors found using a new technique called molecular breast imaging, or MBI, the researchers said ahead of a breast cancer meeting sponsored by the American Society of Clinical Oncology and other groups.
Mammography is used commonly to screen for breast cancer, but about a quarter of women have dense breast tissue -- and mammogram X-rays may not see through this to spot small tumors. Doctors are eager for other methods that perform better.
The study, involving 940 women, is the largest to date to compare MBI to mammography. MBI is still experimental and is not commonly available to women.
The women, considered at high risk for breast cancer due to a family history of the disease, genetic susceptibility or other factors, underwent both screening methods.
With MBI, patients are injected with a radioactive agent that gets absorbed by breast tissue. Cancer cells tend to absorb more of it than healthy cells, and specialized cameras that detect gamma rays from the agent then differentiate tumors from healthy tissue.
"We're certainly not advocating replacing mammography in any way. But we think it (MBI) would have a role as an additional test for those women that aren't served as well by mammography as we would like," Carrie Hruska of the Mayo Clinic in Rochester, Minnesota, who led the study, told reporters.
Using MBI, the ability to see a tumor is not affected by the density of the surrounding breast tissue, so it offers great promise for women whose mammograms may not provide an accurate assessment, Hruska said.
Among the 940 women, 13 tumors were found in 12 women. MBI found 10 and mammography found three, the researchers said.
Dr. Eric Winer of Harvard Medical School and Dana-Farber Cancer Institute in Boston, commenting for the American Society of Clinical Oncology, said between 10 percent and 15 percent of breast cancers cannot be detected using mammograms.
"More and more we may be getting away from one-size-fits-all in terms of screening approaches, and instead think about screening approaches that are directed more to an individual women based on her risk and on the characteristics of her breasts," Winer told reporters in a conference call.
There has been increasing use of costly MRI exams on some women with dense breasts or with high risk for breast cancer.
Hruska said MBI may be a lower-cost alternative. She estimated it would cost about $500 to perform, and expressed hope its availability would increase in the next year.
The technology used special cameras developed by GE Medical Systems and privately held Gamma Medica-Ideas, Hruska said. The study was funded in part by Bristol-Myers Squibb, which provided the radioactive agent, Hruska added.
The radioactive agent typically exits the body in a day.
Hruska said MBI as currently used presents a very low risk of radiation if a woman has it a few times in a lifetime, but the researchers must lower the radiation if the technology begins to be used as a screening test every year or two.

Too much calcium in blood may increase risk of fatal prostate cancer

WINSTON-SALEM, 04 sept 2008– Men who have too much calcium in their bloodstreams may have an increased risk of fatal prostate cancer, according to a new analysis from Wake Forest University School of Medicine and the University of Wisconsin.
"We show that men in upper range of the normal distribution of serum calcium subsequently have an almost three-fold increased risk for fatal prostate cancer," said Gary G. Schwartz, Ph.D., associate professor of cancer biology and of epidemiology and prevention at Wake Forest, a part of Wake Forest University Baptist Medical Center. Such excess calcium can be lowered, he said.
The research appears in the September issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
Co-author Halcyon G. Skinner of the School of Medicine and Public Health at the University of Wisconsin stressed there is "little relationship between calcium in the diet and calcium in serum. So men needn't be concerned about reducing their ordinary dietary intakes of calcium."
Schwartz and Skinner analyzed the results of 2,814 men who participated in the National Health and Nutrition Examination Survey (NHANES-1). Measurement of the amount of calcium in the bloodstreams was determined an average of 9.9 years before prostate cancer was diagnosed.
The researchers focused on the 85 cases of prostate cancer and 25 prostate cancer deaths among the 2,814 men and divided the group into thirds, based on the serum calcium level. "Comparing men in the top third with men in the bottom third, we found a significantly increased hazard for fatal prostate cancer.
"To our knowledge, this is the first study to examine prostate cancer risk in relation to serum calcium," Schwartz and Skinner wrote. "These results support the hypothesis that high serum calcium, or a factor strongly associated with it, such as high serum parathyroid hormone, increases the risk for fatal prostate cancer."
In an interview, Schwartz said that if the relationship between serum calcium and prostate cancer "turns out to be causal, it suggests a means for potentially reducing the risk of fatal disease through medicines that reduce serum levels of calcium and/or parathyroid hormone."
He added, "Both calcium and parathyroid hormone are known to promote the growth of prostate cancer cells in the laboratory."
Skinner said, "The take-home message is that this may offer a simple means to detect men who are at increased risk of fatal prostate cancer."
Schwartz said serum calcium ordinarily is tightly regulated by parathyroid hormone, so there is little variation in an individual's serum calcium over time. "Calcium is basically the current that runs many of the functions of your body. Calcium is important for not only neuromuscular conductions, electrical conductions, but for the conduction of muscles in your heart."
Too little calcium in blood, less than 7 milligrams per deciliter, can cause uncontrolled muscular convulsions or contractions. Too much calcium, above 14 milligrams per deciliter, can cause a coma. "Your body obviously cannot afford to oscillate between convulsions and coma, so the range of serum calcium is tightly controlled."
The upper third of NHANES-1 participants had high normal calcium levels, ranging from 9.9 to 10.5 milligrams per deciliter.
"If confirmed, our study shows that calcium at the high end of normal is associated with a three-fold increased risk of fatal prostate cancer later in life," Schwartz said. But unlike well-known risk factors for prostate cancer such as age, race or family history, which cannot be altered, "a man's serum calcium levels can be."
Several drugs already used in patients with high levels of parathyroid hormone, such as patients with chronic kidney disease, could be used to reduce calcium and/or parathyroid hormone in the blood, he said.
Measurements of serum calcium are routinely collected and are part of most medical visits. Thus, a physician can readily determine whether a man's serum calcium level is at the high end of normal.
"What is particularly exciting – if this study is replicated, and attempts to do so are already in progress – is that it suggests that a man may reduce his risk of fatal prostate cancer by lowering serum levels of calcium and/or parathyroid hormone," he said.

Height linked to risk of prostate cancer development and progression

PHILADELPHIA, 04 sept 2008 – A man's height is a modest marker for risk of prostate cancer development, but is more strongly linked to progression of the cancer, say British researchers who conducted their own study on the connection and also reviewed 58 published studies.
In the September issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, 12 researchers at four universities in England studied more than 9,000 men with and without prostate cancer and estimated that the risk of developing the disease rises by about six percent for every 10 centimeters (3.9 inches) in height a man is over the shortest group of men in the study. That means a man who is one foot taller than the shortest person in the study would have a 19 percent increased risk of developing the disease.
Still, these increases in risk are a lot less than those linked with other established risk factors, such as age, family history of the disease, and race. Because of that, the researchers do not suggest that taller men be screened more often than is typical, or that their cancer treatment be altered.
"Compared to other risk factors, the magnitude of the additional risk of being taller is small, and we do not believe that it should interfere with preventive or clinical decisions in managing prostate cancer," said the study's lead author, Luisa Zuccolo, M.Sc., of the Department of Social Medicine at the University of Bristol. "But the insight arising from this research is of great scientific interest. Little is known on the causes of prostate cancer and this association with height has opened up a new line of scientific inquiry."
For example, Zuccolo says that factors associated with height - not height itself – could be risk factors for progression to fatal prostate cancer, and a plausible mechanism behind this association could be the insulin-like growth factor-1(IGF-1) system, which stimulates cell growth and has been shown to be involved in prostate cancer incidence and progression.
Because some studies have shown a much greater association between height and prostate cancer risk – some between 20 to 40 percent – the researchers then placed their results in the context of available evidence. They conducted a meta-analysis of 58 studies, and found evidence that greater stature is associated with increased prostate cancer risk. But as in their study, the overall effect varied with study design and was modest – a three to 9 percent increase risk of development per 10 centimeters, and five to 19 percent increase in risk for more advanced cancer.
"We do not believe that height itself matters in determining risk of prostate cancer or prostate cancer progression, but we speculate that factors that influence height may also influence cancer and height is therefore acting as a marker for the causal factors," Zuccolo said.

Activity ups seniors' cognitive abilities somewhat

03 sept 2008--Participation in an at-home physical activity program can modestly improve cognition in older adults with memory problems, but who do not have dementia, new research shows.
Previous studies have suggested that physical activity can reduce the odds of mental decline in older adults, the researchers note in this week's issue of the Journal of the American Medical Association, but confirmation from clinical trials has been lacking.
For their study, Dr. Nicola T. Lautenschlager of the University of Melbourne in Victoria, Australia, and colleagues randomly allocated 170 subjects, 50 years of age or older, to a physical activity program or to a comparison "control" group that received usual care.
Participants in the activity program were encouraged to perform moderate-intensity physical activity for at least 50 minutes three times a week. A total of 138 subjects completed an assessment after18-month.
On average, patients in the exercise group performed 142 minutes more physical activity per week than did the controls.
At the 6-month mark, the average score on a standard cognitive test increased by 0.26 points in the activity group, whereas it fell by 1.04 points in the control group. At 18 months, improvements of 0.73 points and 0.04 points were noted in the physical activity and control group, respectively.
"To our knowledge, this trial is the first to demonstrate that exercise improves cognitive function in older adults with subjective and objective mild cognitive impairment," the researchers conclude. Although the improvements were small, they are "potentially important when one considers the relatively modest amount of physical activity undertaken by participants in the study."
SOURCE: Journal of the American Medical Association, September 3, 2008.

Study confirms colorectal cancer screening should start at age 50

Colonoscopy best prevention method for colorectal cancer

Bethesda, MD 03 sept 2008 – Colorectal adenomas, the precursor polyps in virtually all colorectal cancers, occur infrequently in younger adults, but the rate sharply increases after age 50. Additionally, African Americans have a higher rate of proximal, or right-sided, polyps, and may have a worse prognosis for survival if the polyps become cancerous. Therefore, the results of this study further emphasize the importance of colonoscopies, which view the entire colon, for the prevention of colorectal cancer beginning at age 50. The results of this study, which represents the largest investigation, by several-fold, of this kind, were published in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute.

"While colorectal polyps are rare in adults aged 30 to 50, our study reveals an increase in polyp prevalence with age and a dramatic increase in colorectal adenoma incidence occurring in adults over the age of 50," said Francis M. Giardiello, MD, of The John Hopkins University and lead author of the study. "Understanding the natural occurrence of colorectal polyps, especially in younger adults, is important to the development of colorectal cancer prevention strategies."

Findings

Researchers found the prevalence of colorectal polyps in younger adults increased from 1.72 percent to 3.59 percent from age 30 to 50. This rate sharply increased after age 50 with the prevalence of polyps ranging from 10.1 to 12.06 percent in the sixth and ninth decade, respectively. The study results quantified the number of adenomas typically found in people under the age of 50. It is important to note that those with two or more adenomas under 50 years of age represent unusual individuals who might merit closer colonoscopic surveillance for subsequent adenoma development.

In younger adults, adenomas were more prevalent in Caucasians compared to African Americans; however, in older adults, the reverse was true. Regardless of age, adenomas were more prevalent in men than women.

In the general population, left-sided adenomas are most common, but among older adults (age 50+), who have more adenomas, there is a relatively greater prevalence of right-sided adenomas. African Americans in both age groups had predominately right-sided polyps.

Implications for Colorectal Cancer Screening

The use of sigmoidoscopy as a screening test for colorectal cancer does not allow gastroenterologists to view the right-side of the colon to screen for polyps, only the rectum and the lower end of the colon. If a polyp or abnormality is found, patients may require a regular colonoscopy for further evaluation. Right-sided adenomas cannot be viewed using a sigmoidoscopy.

Colonoscopy, which provides the most comprehensive view of the colon, is the definitive test for colorectal cancer screening. Colonoscopies allow gastroenterologists to view the entire colon and rectum for polyps or cancer and during the same exam remove pre-cancerous polyps. It is the test most gastroenterologists recommend as the single best screening exam for colorectal cancer. It is the only method that combines both screening and prevention (by removal of pre-cancerous polyps).

Study Design

The study evaluated the large intestine of 3,558 autopsy subjects, aged 20-89, that had colorectal cancer undetected or unsuspected during life. Subjects were categorized by sex, race and age in 10 year groups. Location and number of colorectal adenomas detected was measured by using epidemiologic autopsy in individuals; results were standardized to the general population. The study's researchers evaluated the large intestine of 1,001 individuals undergoing necropsy between the ages of 20 and 49 for the presence of adenomas.

Obesity not a red flag for spotting diabetes

03 sept 2008--Obese people with diabetes are just as likely to go undiagnosed as their slimmer peers with the disease, Harvard Medical School researchers report.

It's well recognized that obesity increases the likelihood of developing diabetes, yet "obesity does not increase the likelihood that an individual's diabetes will be diagnosed," Dr. Christina C. Wee and her colleagues from Harvard and Beth Israel Deaconess Medical Center in Boston report.

There is no consensus on who should be screened for diabetes, Wee and her team note in their report in the medical journal Diabetes Care. Early diagnosis of diabetes is particularly important for obese people, they add, because research shows they are less likely to be offered the preventive care that can help stave off serious complications of the disease.

To investigate the impact of a person's body mass index (BMI) on their odds of having undiagnosed diabetes, the researchers looked at 5,514 people participating in the 1999-2004 National Health and Nutrition Examination Survey.

Almost 10 percent of the study participants had diabetes, and 28 percent of them had not been diagnosed with the disease. A person's BMI made no difference from a statistical standpoint in whether or not they went undiagnosed; 22 percent of normal weight people with diabetes were undiagnosed, 32 percent of overweight people were, and about 33 percent of obese people were.

Further research is needed to understand whether including overweight and obesity in diabetes screening initiatives may be beneficial for public health, Wee and her colleagues add. Meanwhile, they add, "Clinicians and policy makers may want to consider the underlying risk of diabetes associated with body weight in making decisions concerning whom should be screened for diabetes."

SOURCE: Diabetes Care, September 2008.

Breast Cancer Drug Not Tied to Cognitive Decline: Study

03 sept 2008 -- Contrary to previous study results, the cancer prevention drug anastrozole does not appear to cause impairment of cognitive performance, a new study found.

Anastrozole has been shown to be superior to tamoxifen in preventing breast cancer recurrence in postmenopausal women. But some "cross-sectional" studies have suggested that endocrine therapies such as anastrozole are associated with poorer performance on verbal memory and processing tasks.

For the new study, published in the October edition of The Lancet Oncology, researchers randomly assigned postmenopausal women to receive anastrozole or a placebo daily for five years.

Before the study began, and for six months and 24 months after starting treatment, a subset of 227 of the women underwent tests to measure their cognitive performance, including auditory verbal tasks, logical memory tasks, spatial span tests, and verbal fluency assessments.

There was no difference between the anastrozole or placebo groups at six months or 24 months in changes in attention or memory, or in the number of women who experienced cognitive decline in three or more cognitive tasks.

The only difference between the groups was that at the 24-month time point, significantly more women in the anastrozole group reported experiencing hot flushes.

The authors of the study pointed out that more research is needed to determine the longer-term effects of anastrozole, but said their findings were good news for women who take the medication.

"These findings should be reassuring in the short term for postmenopausal women being treated with anastrozole, their clinicians and carers," they wrote.

This study was part of the International Breast Intervention Study.

More information

The U.S. National Cancer Institute has more about anastrozole.

All types of sexual activity carry some STD risk

03 sept 2008--Sexual activity other than intercourse carries some risk of sexually transmitted disease, and doctors should make sure their patients understand that, according to the American College of Obstetricians and Gynecologists (ACOG).

Many people may engage in "noncoital" sexual activities such as oral sex, mutual masturbation and anal sex to prevent pregnancy and cut the risk of STDs. However, all of these sex acts come with some degree of STD risk, and it's still important for people to protect themselves, according to an ACOG expert committee.

"Most people, including adolescents, are unlikely to use condoms during oral sex, which places them at risk for acquiring an STD," Dr. Richard Guido, one of the report authors, said in an ACOG statement. "This unlikelihood is partly because of a greater perceived safety compared with intercourse."

Writing in the journal Obstetrics & Gynecology, the panel advises doctors to ask patients -- adults and teenagers -- about all of their sexual activities, and to counsel them on how to reduce their STD risks. Although this "is a sensitive issue to address for both patients and physicians, it's important to discuss sexuality frankly and without judgment so that we can help our patients fully protect themselves against STDs," Guido added.

While oral sex is generally safer than vaginal or anal sex, the ACOG committee notes, it is not without risk. The viruses that cause genital herpes, genital warts and hepatitis can all be transmitted through oral sex. The same is true of the bacterial STDs syphilis, gonorrhea and chlamydia.

When it comes to HIV transmission, receptive anal sex carries the highest risk, followed by receptive vaginal sex, according to ACOG. However, there have been cases of HIV linked to oral sex.

"Noncoital sexual activity is not necessarily 'safe sex'," Guido and his colleagues write in the report.

They advise "correct and consistent" condom use for all types of sexual activity, but especially vaginal and anal sex. Staying in a mutually monogamous relationship, and getting tested for STDs before starting a new relationship, are among the other ways to curb STD transmission. Another precaution, the committee notes, is to clean sex toys between uses.

It's recommended that all sexually active women age 25 or younger be screened for chlamydia once a year, while all sexually active teenagers should be screened for gonorrhea. Other screening tests are done based on individuals' STD risk factors or any symptoms they may have.

The ACOG committee points out that lesbian women should be screened on the same basis as heterosexual women.

"Most lesbians have been sexually active with men at some point," Guido said. "Even without this sexual history, there are some STDs that can be transmitted between two women during sexual activity."

SOURCE: Obstetrics & Gynecology, September 2008.

Doubts Grow Over Flu Vaccine in Elderly

By BRENDA GOODMAN
02 sept 2008--The influenza vaccine, which has been strongly recommended for people over 65 for more than four decades, is losing its reputation as an effective way to ward off the virus in the elderly.
A growing number of immunologists and epidemiologists say the vaccine probably does not work very well for people over 70, the group that accounts for three-fourths of all flu deaths.
The latest blow was a study in The Lancet last month that called into question much of the statistical evidence for the vaccine’s effectiveness.
The authors said previous studies had measured the wrong thing: not any actual protection against the flu virus but a fundamental difference between the kinds of people who get vaccines and those who do not.
This contention is far from universally accepted. And even skeptics say that until more effective measures are found, older people should continue to be vaccinated, because some protection against the flu is better than none.
Still, the Lancet article has reignited a longstanding debate over claims that the vaccine prevents thousands of hospitalizations and deaths in older people. “The whole notion of who needs the vaccine and why is changing before our eyes,” said Peter Doshi, a doctoral candidate at M.I.T. who published a paper on the historical impact of influenza in May in The American Journal of Public Health.
The Lancet paper, by Michael L. Jackson and colleagues at the Group Health Center for Health Studies in Seattle, was based on an analysis of medical charts of thousands of elderly members of an H.M.O.
The study found that people who were healthy and conscientious about staying well were the most likely to get an annual flu shot. Those who are frail may have trouble bathing or dressing on their own and are less likely to get to their doctor’s office or a clinic to receive the vaccine. They are also more likely to be closer to death.
Dr. David K. Shay of the Centers for Disease Control and Prevention, a co-author of a commentary that accompanied Dr. Jackson’s study, agreed that these measures of health and frailty “were not incorporated into early estimations of the vaccine’s effectiveness” and could well have skewed the findings.
Not everyone is sold on the significance of the Lancet study. “I think this is another study that provides interesting findings and raises questions,” said Dr. Kristin Nichol, chief of medicine at the Veterans Affairs hospital in Minneapolis. “I don’t think we know yet what the final word is on influenza vaccinations in the elderly.
“I really feel, and I feel very strongly about this, that the public health message should be that vaccines are effective,” she continued. “I don’t think that science is necessarily best hashed out in the media.”
Dozens of studies since 1960 have supported the view that the vaccine is a powerful protector of the elderly, cutting their risk of dying in winter from any cause by almost 50 percent and reducing the risk of hospitalization by nearly 30 percent.
Those findings came from observational studies, in which scientists make inferences about the effect of a treatment on a population by comparing what happens to a group that has the treatment with what happens to an apparently similar group that does not.
There has been only one large study that compared the flu vaccine with a placebo for two random groups of older people in which neither the patients nor the scientists knew which group was receiving which injection. It came to a different conclusion from the observational studies.
Conducted by Dutch researchers and published in 1994 in The Journal of the American Medical Association, it found that in those 60 to 69, the vaccine prevented influenza about 57 percent of the time. In those over 70, the vaccine prevented the flu just 23 percent of the time, though the estimate is imprecise because the study was not designed to look at this age group.
But the influenza vaccine was never put through more placebo-controlled trials, which are considered the gold standard in medical evidence. “I think the evidence base we have leaned on is not valid,” said Lone Simonsen, an epidemiologist and visiting professor at the George Washington University School of Public Health and Health Services in Washington who was not connected with the Lancet study.
In 2005, Dr. Simonsen, who was then at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., published a paper in The Archives of Internal Medicine that found something odd: even though the percentage of older people who got an annual flu shot more than tripled from 1980 to 2001, there was no corresponding drop in the death rate.
That paper included one of the first estimates of how many deaths are actually caused by the flu — a number hard to pin down because doctors seldom confirm flu in their patients with lab tests. Using a statistical model and the best available data, Dr. Simonsen found that influenza probably causes just 5 to 10 percent of all winter deaths in the elderly. But earlier studies had found that the flu vaccine cut an elderly person’s risk of dying by 50 percent.
“You don’t have to do a whole lot of math to realize that doesn’t add up,” said Dr. Lisa A. Jackson of the Group Health Center for Health Studies in Seattle, who has also studied the effectiveness of the flu vaccine in the elderly.
Dr. Jackson at first tried to tease out underlying differences between vaccinated and unvaccinated elderly people by using medical codes — a numerical shorthand that doctors use to classify and record what is wrong with their patients. She and other researchers reasoned that patients with codes for cancer or heart disease, for example, might be very sick, thus skewing the results. When they adjusted for those codes, however, the differences between the vaccinated and unvaccinated groups became even more pronounced. The vaccine looked even more protective.
It was Michael L. Jackson’s thesis project, at the University of Washington, that revealed the flaw in using the codes to differentiate patients.
For the project, Mr. Jackson (no relation to Lisa Jackson) and three other researchers spent almost three years reading medical charts and examining X-rays. They discovered that health-conscious people were more likely to get medical codes for things like heart disease and cancer simply because they went to the doctor more often. But when Mr. Jackson adjusted for measures of frailty — things like lung function, whether people needed help bathing or dressing, and what kinds of medications they took — he found that vaccination had little effect on older people’s risk for pneumonia, the most dangerous complication of the flu.
That finding has a biological basis. Vaccines work by priming the immune system to recognize and respond to incoming threats. Because the immune system slows down with age, older adults do not respond as well to vaccines as younger adults.
A recent study by Dr. Wilbur H. Chen and colleagues at the Center for Vaccine Development at the University of Maryland School of Medicine found that elderly participants needed four times the amount of antigens given in a standard dose of the flu vaccine to have the same kind of immune response as healthy adults under 40. They presented their findings in May at the Annual Conference on Vaccine Research in Baltimore.
Despite these findings, Dr. Shay said the C.D.C. had no plans to change its vaccine recommendations, though he added that the agency had financed studies to look for more effective influenza vaccines for the elderly.
Dr. Simonsen, the epidemiologist at George Washington, said the new research made common-sense infection-control measures — like avoiding other sick people and frequent hand washing — more important than ever. Still, she added, “The vaccine is still important. Thirty percent protection is better than zero percent.”

Brain imaging links chronic insomnia to reversible cognitive deficits without changes in behavior

Westchester, Ill., 02 sept 2008 — A neuroimaging study in the Sept. 1 issue of the journal Sleep is the first to find that cognitive processes related to verbal fluency are compromised in people with insomnia despite the absence of a behavioral deficit. These specific brain function alterations can be reversed, however, through non-pharmacological treatment with sleep therapy.
Results of functional magnetic resonance imaging (fMRI) scanning during verbal fluency tasks show that people with insomnia have less activation than controls in the left medial prefrontal cortex and the left interior frontal gyrus, two fluency-specific brain regions. However, participants with insomnia generated more words than controls on both the category fluency task (46.4 words compared with 38.7 words) and the letter fluency task (40.1 words compared with 32.7 words).
"It was surprising to see that the patients performed at a higher level than the control group, but showed reduced brain activation in their fMRI results," said principal investigator Ysbrand Der Werf, PhD, of the Netherlands Institute for Neuroscience in Amsterdam. "The success during the task may reflect a conscious effort to counteract the effect of poor sleep."
Results from post-treatment neuroimaging shows that cognitive abnormalities recovered for insomnia patients who received sleep therapy, but not for those assigned to a wait-list group. Participants in the sleep therapy group also generated more words on the verbal fluency tasks after treatment than members of the wait-list group, although the results did not achieve statistical significance.
According to the authors, these results should encourage the use of sleep therapy in clinical practice as a low-cost, non-pharmacological intervention for insomnia.
The study included 21 chronic insomnia patients with an average age of 61 years and 12 healthy controls with an average age of 60 years who were matched for age, sex and education. Insomnia was defined as "chronic" if it had lasted for at least 2.5 years. Participants underwent fMRI scanning during the performance of verbabal fluency tasks between 5 p.m. and 8:30 p.m.
Insomnia patients then were randomly assigned to a six-week long sleep therapy group or a wait-list group. Therapy involved a combination of sleep restriction, multifaceted cognitive-behavior therapy, morning and late afternoon bright-light exposure and body temperature manipulations. After six weeks, fMRI scanning was repeated on both treatment groups during the same verbal fluency tasks.
###
A media fact sheet about insomnia is available from the AASM at http://www.aasmnet.org/Resources/FactSheets/Insomnia.pdf. Information about insomnia for patients and the public is available from the AASM at http://www.sleepeducation.com/Disorder.aspx?id=6.
Sleep is the official journal of the Associated Professional Sleep Societies, LLC, a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.
For a copy of the study, "Prefontal Hypoactivation and Recovery in Insomnia," or to arrange an interview with an AASM spokesperson, please contact Kelly Wagner, AASM public relations coordinator, at (708) 492-0930, ext. 9331, or kwagner@aasmnet.org.

Playing, and even watching, sports improves brain function

02 sept 2008--Being an athlete or merely a fan improves language skills when it comes to discussing their sport because parts of the brain usually involved in playing sports are instead used to understand sport language, new research at the University of Chicago shows.
The research was conducted on hockey players, fans, and people who'd never seen or played the game. It shows, for the first time, that a region of the brain usually associated with planning and controlling actions is activated when players and fans listen to conversations about their sport. The brain boost helps athletes and fans understanding of information about their sport, even though at the time when people are listening to this sport language they have no intention to act.
The study shows that the brain may be more flexible in adulthood than previously thought. "We show that non-language related activities, such as playing or watching a sport, enhance one's ability to understand language about their sport precisely because brain areas normally used to act become highly involved in language understanding," said Sian Beilock, Associate Professor in Psychology at the University of Chicago. She is lead author of the paper, "Sports Experience Enhances the Neural Processing of Action Language," to be published Tuesday, September 2 in the on-line issue of the Proceedings of the National Academy of Sciences.
"Experience playing and watching sports has enduring effects on language understanding by changing the neural networks that support comprehension to incorporate areas active in performing sports skills," she said.
The research could have greater implications for learning. It shows that engaging in an activity taps into brain networks not normally associated with language, which improves the understanding of language related to that activity, Beilock added.
For the study, researchers asked 12 professional and intercollegiate hockey players, eight fans and nine individuals who had never watched a game to listen to sentences about hockey players, such as shooting, making saves and being engaged in the game. They also listened to sentences about everyday activities, such as ringing doorbells and pushing brooms across the floor. While the subjects listened to the sentences, their brains were scanned using functioning Magnetic Resonance Imaging (fMRI), which allows one to infer the areas of the brain most active during language listening.
After hearing the sentences in the fMRI scanner, subjects performed a battery of tests designed to gauge their comprehension of those sentences.
Although most subjects understood the language about everyday activities, hockey players and fans were substantially better than novices at understanding hockey-related language.
Brain imaging revealed that when hockey players and fans listen to language about hockey, they show activity in the brain regions usually used to plan and select well-learned physical actions. The increased activity in motor areas of the brain helps hockey players and fans to better understanding hockey language. The results show that playing sports, or even just watching, builds a stronger understanding of language, Beilock said.
###
Joining Beilock in this research were Howard Nusbaum, Professor of Psychology at the University; Steven Small, Professor of Neurology and Psychology at the University; and Beilock's Ph.D. students Ian Lyons and Andrew Mattarella-Micke.

Study: Bypass better than stents in long term

By MARIA CHENG
02 sept 2008--For heart patients with clogged arteries, the choice between bypass surgery or an angioplasty may come down to one question: How many procedures would you like to have?
In research presented Monday at the European Society of Cardiology meeting in Munich, experts concluded that while bypass surgery and angioplasty offer comparable results, patients who have angioplasties are twice as likely to require another procedure within a year.
"If you don't want to have another heart operation for at least a decade, you should pick the surgery," said Dr. Heinz Drexel, professor of medicine at the University of Innsbruck in Austria and spokesman for the European Society of Cardiology. Drexel was not connected to the research.
"But that means you have to have your chest cracked open," he said.
When arteries become blocked, doctors have two main options. Traditionally they have done a bypass surgery, which reroutes blood vessels to detour around blockages.
But in recent years, angioplasties have become increasingly popular. An angioplasty is a non-surgical procedure where a balloon is pushed into a blood vessel to flatten the blockage, leaving a stent to prop the artery open.
In the study results announced Monday, European doctors compared the effectiveness of open-heart surgery versus angioplasty in a trial of more than 3,000 patients in Europe and the United States.
About a third of the patients had medical conditions that required surgery. The remaining patients were randomly assigned to receive either surgery or an angioplasty.
The study was paid for by Boston Scientific, makers of heart stents.
After one year, researchers found that the death rate among the two groups was virtually the same: 7.7 percent among surgery patients and 7.6 percent among angioplasty patients.
In patients who had an angioplasty, nearly 14 percent needed another procedure after a year, compared with about 6 percent of surgery patients.
But patients who had surgery had about a 2 percent stroke risk versus nearly zero risk for patients who had an angioplasty. Doctors said that any surgery had an inherent stroke risk, compared with an angioplasty.
In January, a study published in the New England Journal of Medicine found that bypass surgery was still the best option for heart patients with more than one clogged artery.
"Surgery still comes out as the winner in a head-to-head trial," said Dr. Douglas Weaver, president of the American College of Cardiology, who was unconnected to the research.
"This comes down to a conversation with patients and making sure they know that with an angioplasty, there will be a higher rate of revascularization," he said, referring to the need for repeat procedures.
Patients typically need at least a month to fully recover from an open-heart surgery, a five-hour long operation under general anesthesia.
Angioplasty patients, however, are often up and walking around after three days.
"You invest more in terms of recuperation with surgery," said Dr. Tim Gardner, president of the American Heart Association. "But the advantage is durability."
When drug-coated stents were first introduced in 2003, they became the fastest-selling medical device in recent history. Doctors thought that the tiny tubes, which leak drugs to prevent tissue regrowth, would make angioplasty a much better alternative to surgery for patients.
But in 2006, studies began to emerge showing that patients with the drug-coated stents were more likely to develop potentially fatal blood clots months and even years after they were implanted.
Stent sales plummeted and doctors have become more wary of their use, saving them only for certain patients with no other options.
Doctors cautioned that more data is still needed about the pros and cons of bypass surgery versus angioplasties, and that patients needed to be tracked for at least five years.
"This only tells us what happens after one year," Drexel said. "We need to wait for at least five years to get a good answer about which therapy is really better."

Fish oil appears to help against heart failure

By MARIA CHENG
02 sept 2008--Fish oil supplements may work slightly better than a popular cholesterol-reducing drug to help patients with chronic heart failure, according to new research released Sunday.
Chronic heart failure is a condition that occurs when the heart becomes enlarged and cannot pump blood efficiently around the body.
With few effective options for heart failure patients, the findings could give patients a potential new treatment and could change the dietary recommendations for them, said Dr. Jose Gonzalez Juanatey, a spokesman for the European Society of Cardiology, who was not connected to the research.
"This reinforces the idea that treating patients with heart failure takes more than just drugs," Juanatey said.
The study findings were published online in the medical journal The Lancet on Sunday. They were simultaneously announced at a meeting of the European Society of Cardiology in Munich.
"With a lot of these patients, you have no other choice," said Dr. Helmut Gohlke, a cardiologist at the Heart Centre in Bad Krozingen, Germany. "They've tried other treatments and are at the end of the road."
Italian researchers gave nearly 3,500 patients a daily omega-3 pill, a prescription-formulation pill derived from fish oils, produced by Norway's Pronova BioPharma.
But doctors said people should get the same benefits from taking cheaper options like fish oil supplements — or just eating more oily fish like salmon.
Roughly the same number of patients were given placebo pills. Patients were followed for an average of four years.
In the group of patients taking the fish oil pills, 1,981 died of heart failure or were admitted to the hospital with the problem. In the patients on placebo pills, 2,053 died or were admitted to the hospital for heart failure.
In a parallel study, the same team of Italian doctors gave 2,285 patients the drug rosuvastatin, also known as Crestor, and gave placebo pills to 2,289 people. Patients were then tracked for about four years. The doctors found little difference in heart failure rates between the two groups.
Comparing the results from both studies, the researchers concluded that fish oil is slightly more effective than the drug because the oil performed better against a placebo than did Crestor.
"It's a small benefit, but we should always be emphasizing to patients what they can do in terms of diet that might help," said Dr. Richard Bonow, chief of cardiology at Northwestern University Hospital in Chicago and past president of the American Heart Association.
Both studies were paid for by an Italian group of pharmaceuticals including Pfizer Inc., Sigma Tau SpA and AstraZeneca PLC.
Omega-3 fatty acids from fish such as salmon and tuna have long been proven to offer health benefits like protecting the heart and brain, though scientists aren't exactly sure how.
Bonow said that since cell membranes are made of fatty acids, fish oils may help to replace and strengthen those membranes with omega-3.
Fish oils also are thought to increase the body's good cholesterol levels, as well as possibly stabilizing the electrical system in heart cells, to prevent abnormal heart rhythms.
In contrast, statins act on the body's bad cholesterol, which may not have a big impact on heart failure.
Previous studies that investigated the benefits of omega-3 fatty acids have largely been observational, and have lacked a direct comparison to a placebo. It has also been unknown whether taking fish oil supplements would be as good as eating fish.
"This study changes the certainty of the evidence we have about fish oils," said Dr. Douglas Weaver, president of the American College of Cardiology.
Weaver said that guidelines in the United States would likely change to recommend that more heart patients eat more fish or take supplements. "This is a low-tech solution and could help all patients with cardiovascular problems."

Landmark study opens door to new cancer, aging treatments Wistar Institute researchers decipher telomerase structure

PHILADELPHIA, 01 sep 2008—Researchers at The Wistar Institute have deciphered the structure of the active region of telomerase, an enzyme that plays a major role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies.
Researchers have attempted for more than a decade to find drugs that shut down telomerase—widely considered the No. 1 target for the development of new cancer treatments—but have been hampered in large part by a lack of knowledge of the enzyme's structure.
The findings, published online August 31 in Nature, should help researchers in their efforts to design effective telomerase inhibitors, says Emmanuel Skordalakes, Ph.D., assistant professor in Wistar's Gene Expression and Regulation Program, who led the study.
"Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells," Skordalakes says. "That means a drug that deactivates telomerase would likely work against all cancers, with few side effects."
The study elucidates the active region of telomerase and provides the first full-length view of the telomerase molecule's critical protein component. It reveals surprising details, at the atomic level, of the enzyme's configuration and how it works to replicate the ends of chromosomes—a process critical to both tumor development and the aging process.
Achieving immortality
In humans, telomerase adds multiple repeats of a short DNA sequence to the ends of chromosomes, known as telomeres, thus preventing damage and the loss of genetic information during cell division.
When telomerase is dormant, telomeres shorten each time a cell divides, leading eventually to genetic instability and cell death. By preserving chromosomes' integrity, telomerase allows cells to continue living and dividing. The enzyme is active in cells that multiply frequently, such as embryonic stem cells, but is switched off almost entirely in normal adult cells to prevent the dangers of runaway cell proliferation.
Cancer cells, however, often regain the ability to activate telomerase, which has been implicated in 90 percent of human tumors. The enzyme permits cells to replicate indefinitely and achieve the cellular "immortality" that is the hallmark of cancer. Deactivating telomerase would stop tumor growth.
In addition to its role in cancer, telomerase holds significant implications for the development of therapies to combat aging and other age-related diseases. Finding ways to activate telomerase under controlled conditions and allow some cells to begin dividing again could result in healthier, younger-looking tissue that lives longer.
An elusive enzyme
Telomerase is a complex structure made up of multiple protein domains and a stretch of RNA, which contains the template the enzyme uses to synthesize telomeres.
Last year, Skordalakes and his team solved the structure of a key segment of the molecule—the so-called TRBD domain, where RNA binding occurs. However, the complexity of telomerase has proved a roadblock to determining the enzyme's overall architecture—a goal pursued by researchers worldwide for more than 15 years.
To perform the necessary studies, scientists first must gather large quantities of the enzyme in a specific conformation. Because the complex structure of telomerase most likely allows it to change configuration, that process has been challenging, Skordalakes says.
To find sufficient quantities of the enzyme for the study, Skordalakes and his team looked beyond commonly relied-on sources such as humans and yeast. By screening a wide variety of organisms, including protozoa and insects, they discovered that a gene from the red flour beetle could produce telomerase in copious amounts, and a stable form.
"That was really the breakthrough," Skordalakes says. "Once we found that the gene from this organism expressed the protein in the quantities we needed, we were able to move quickly."
The researchers used X-ray crystallography, a technique that analyzes the diffraction patterns of X-rays beamed at crystals of a molecule, to determine the three-dimensional structure of the enzyme's active region—the catalytic component called telomerase reverse transcriptase protein, or TERT.
The study revealed surprising features, including the fact that the molecule's three domains are organized into a doughnut shape, an unexpected configuration. Knowledge of the structure allowed the researchers to create a model of the enzyme's function.
"It's extremely exciting," Skordalakes says. "For the first time, we can see how telomerase assembles at the end of chromosomes to initiate telomere replication."
Looking ahead
Skordalakes plans to further study TERT and search for new telomerase inhibitors that could become cancer therapies. He also will look at modifying existing drugs. Previous attempts to target telomerase have fallen flat, but knowledge of the enzyme's structure will help researchers to determine the limitations of existing agents and make them more effective.
Skordalakes began his studies of telomerase when he joined The Wistar Institute in 2006 and established his first laboratory. "I've always been interested in understanding, on a molecular level, the function of protein nucleic acid assemblies and using that information in the treatment of human disease," he says. "Telomerase, because of its important role in cancer and aging, was an obvious target for me."
He says though the process was frustrating at times, his team was determined to solve the structure. "It required a lot of perseverance and effort, but we really wanted to do this," he says.
###
Wistar's Andrew J. Gillis and Anthony P. Schuller assisted with the study.
The research was supported in part by the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health and the Ellison Medical Foundation.
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today's Discoveries – Tomorrow's Cures. On the Web at http://www.wistar.org/.

Experts set plan to tackle global cancer crisis

By Stephanie Nebehay
01 sep 2008--Cancer specialists set a plan on Sunday to stem the rise in deaths from cancer by 2020 and ensure that all patients suffering in the late stages of the disease can access painkillers.
The road map laid down by 63 experts and policy-makers includes more screening and early detection programs, especially in poor countries where treatment can be hard to come by.
Tobacco and alcohol consumption as well as obesity levels must be curbed for cancer rates to drop, according to the panel.
Its declaration was presented at the end of a four-day World Cancer Congress hosted by the International Union against Cancer
(IUCC).
Some 25 million people worldwide live with various forms of cancer and 7.9 million died of it last year.
"We know that one-third of the cancer burden could be cured if there were early detection and proper access to medical help," Mary Robinson, who chaired the panel, told reporters.
Another third of cases could be prevented through control of tobacco, pollution and other hazards, according to Robinson, a former president of Ireland and United Nations High Commissioner for Human Rights.
Survival rates have improved in rich countries as cancers
are detected early and treated.
But lifestyle changes means cancer is affecting more people and claiming more lives in the developing world, which accounts for three out of four global deaths, according to the IUCC.
PAIN CONTROL
The new plan calls for all countries to upgrade their cancer control programs. Universal vaccinations for hepatitis B and human papilloma virus, which cause liver and cervical cancer respectively, should also be extended, the specialists said.
Some 4 million cancer patients lack access to opioids such as morphine to alleviate their pain, according to Margaret Chan, director-general of the World Health Organization.
Addressing this, the declaration calls for "effective pain control measures" to be available to all cancer patients.
"This is probably one of the most important targets because there is no excuse. Intravenous morphine is very, very cheap. So every country in the world can buy that," said Franco Cavalli, the IUCC's outgoing president.
Robinson, who serves on the board of the GAVI Alliance, which works to bring vaccines to the world's poorest areas, said that each year 500,000 women are diagnosed with cervical cancer and about 300,000 die from it.
Merck & Co.'s Gardasil and GlaxoSmithKline's Cervarix are vaccines that protect people against some strains of the cancer-causing virus, but the $360 pricetag for the three shots needed for full coverage is too expensive for many.
Researchers told the talks that vaccines against cervical cancer should be more cost effective. Subsidies could be needed for developing countries, they said, suggesting a price of $10 to $25 per girl, depending on the area.

New gene clues emerge for leukaemia, obesity, bowel disease

01 sep 2008--Teams of doctors on Sunday said they had uncovered genetic flaws that separately boost the risk of a common form of leukaemia and bowel disease in children and may also influence obesity and fertility.
The work is reported in three different studies, published by the journals Nature Genetics and Nature Medicine.
A team led by Richard Houlston of Britain's Institute of Cancer Research found six genetic variants that increase vulnerability to chronic lymphocytic leukaemia (CLL), which accounts for roughly a quarter of all leukaemia cases.
The variants occur in genes that play a role in the proliferation of so-called B cells, a type of white blood produced in the bone marrow.
Individually, these variants each contribute to a modest increase in the risk of CLL, but a person with all six faces an eight-fold increase.
Meanwhile, investigators in the United States found that a gene switched on by leptin -- a hormone that tells the brain when the body has sufficient nutrition -- is involved in appetite disorder and infertility.
The discovery was found in the brain of mice, but there are likely to be strong similarities in humans, the authors said.
"This gene is crucial to the daisy chain of signals that run between body fat and brain," lead researcher Marc Montminy of the Clayton Foundation Laboratories for Peptide Biology, said in a press release.
"It likely plays a pivotal role in how much we, as humans, eat and whether we have offspring."
Variations of the gene, called TORC1, could play a part in obesity and infertility, as they could send the wrong signals to the brain as to whether food is needed and whether the body has sufficient energy stores for reproduction.
A third study, entailing a trawl through the genetic code of thousands of people, netted two new genes involved in childhood inflammatory bowel disease (IBD), a painful condition that includes Crohn's disease and ulcerative colitis.
Genomics -- as genetic analysis is called -- is one of the most eagerly explored frontiers of medicine today.
Finding genes that cause or amplify a disease opens up pathways for diagnostic tools to help identify people at risk from the ailment.
It also, more distantly, opens up avenues for potential drugs to block or reverse the gene's malfunction.

Sex hormones link to heart risk

01 sep 2008--New research led by University of Leicester into why men are more prone to heart disease
Men are more prone to – and likely to die of - heart disease compared with women of a similar age – and sex hormones are to blame, according to a new University of Leicester led study
The findings of a study by Dr Maciej Tomaszewski, New Blood Lecturer in Cardiovascular Medicine in the Department of Cardiovascular Sciences at the University of Leicester, suggest that this "male disadvantage" may be related to the sex-specific effects of naturally occurring sex hormones.
The research by Dr Tomaszewski and his colleagues, which has been published on line in the journal Atherosclerosis, involved 933 men aged, on average, 19 years, from the Young Men Cardiovascular Association study. The researchers looked at ways that the sex hormones - estradiol, estrone, testosterone and androstenedione - interacted with three major risk factors of heart disease (cholesterol, blood pressure and weight).
They found that two of these sex hormones (estradiol and estrone, called together estrogens) are linked to increased levels of bad cholesterol (LDL-cholesterol) and low levels of good cholesterol (HDL-cholesterol) in men.
This suggests that certain sex hormones may be important risk factors of heart disease in men, even before they present symptoms of coronary artery disease or stroke.
Dr Tomaszewski commented: "We hypothesised that circulating concentrations of sex hormones were associated with cardiovascular disease risk factors in men long before any apparent manifestations of cardiovascular disease such as stroke or myocardial infarction".
"We examined associations of circulating estrogens (estradiol and estrone) as well as androgens (testosterone and androstenedione) with major cardiovascular risk factors (lipids, blood pressure, body mass) in 933 young (median age – 19 years), apparently healthy men.
"Our studies showed that one of the sex hormones - estradiol - was associated positively with total cholesterol and negatively with HDL-cholesterol. Circulating concentrations of another sex hormone - estrone - showed strong positive associations with both total cholesterol and LDL-cholesterol.
"Thus, men with the highest concentrations of estrone and estradiol may have the highest level of cardiovascular risk as their levels of detrimental LDL-cholesterol are high whilst their cardio-protective HDL-cholesterol is low.
"Most importantly, the demonstrated associations between cholesterol and estrogens were independent of other sex hormones (testosterone and androstenedione), age, body weight, blood pressure and other potential confounding factors.
"Our data suggest that higher levels of estrogens may have negative influence on lipid profile in men early in life, before the apparent onset of cardiovascular disease.
"Why natural endogenous estrogens that are generally seen as cardio-protective in women increase cardiovascular risk in men remains to be elucidated. Future prospective studies are needed to confirm that higher levels of endogenous estrogens in youth increase the risk of heart disease later in man's life.
"A number of other investigations on sex-specific aspects of cardiovascular disease are in progress in our Department and I am sure that we will be able to continue providing information in this area of research in the future."

Neurogenesis in the adult brain: The association with stress and depression

01 sep 2008--The brain is the key organ in the response to stress. It reacts in a complex, orchestrated manner that is related to the activation and inhibition of neural structures involved in sensory, motor, autonomic, cognitive and emotional processes. It is the brain which finally determines what in the world is threatening and might be stressful for us, and which regulates the stress responses that can be either adaptive or maladaptive. Chronic stress can affect the brain and lead into depression: Environmental stressors (e.g. job and family situation, neighborhood) and especially stressful life events such as trauma or abuse are amongst the most potent factors to induce depression. Since the development of novel approaches to antidepressant treatment is based upon an improved neurobiological understanding of this condition, new information about the cellular changes that take place in the brain is required.
Depression: a growing public health burden
Depression is a chronic, recurring, multifactorial, and life-threatening disorder, which represents a collection of psychological, neuroendocrine, physiological and behavioural symptoms. Chronicity and frequency of these symptoms constitute the clinical condition. Depressive disorders affect up to 20% of people at some time in their life. In primary care, an estimated 20󈞞% of patients suffer from depression, but often are not diagnosed correctly (Wittchen, 2000).
Depressive disorders are among the most prevalent illnesses worldwide, producing significant public health and socioeconomic problems (WHO, 2001). The immense costs of depression account for approximately 1% of the gross domestic product in Europe (approximately 100 billion Euro). Depression is affecting more than 120 million people globally, and is set to rise to become one of the leading causes of disability, second only to cardiovascular disease, by the year 2015.
Brain changes induced by stress and depression
The areas of the brain that are most affected by the changes caused by depression are the prefrontal cortex, amygdala and hippocampus, which are central to emotion, memory and learning. Structural and functional changes as a consequence of stress and/or major depression are a reduction in volume, neuronal size and density, associated with changes in cerebral blood flow and glucose metabolism (see figure 1). In addition, there is a reduced density of glial support cells that are instrumental in the communication between nerve cells, which is particularly relevant to the reduced volume of the prefrontal cortex and the hippocampus. The shrinkage might explain some of the emotional changes observed in people with depression.
Neurogenesis in the adult brain
The ´stress hypothesis´ of affective disorders has stimulated the development of putative animal models of depression. Animal models today are generally regarded as invaluable in preclinical research on human psychopathology, and are thus of prime interest in studying the pathophysiology of depression and specific responses to antidepressant drug treatments. The discovery that the adult nervous system is capable of replacing its cells has attracted considerable interest in the scientific community. Up to now, neural networks in adults have been thought to be fixed and immutable, without the potential to regenerate: This assumption was prominently pronounced by the famous Spanish neuroscientist Santiago Ramon y Cajal, who postulated that „everything may die, nothing may regenerate" (Cajal, 1928). Current research has overcome this view and has shown that the formation of new nerve cells (=neurogenesis) also takes place in the adult brain. Neurogenesis can be modified by positive modulators such as learning, physical exercise, and hormonal influence, as well as negative modulators such as acute and chronic stress.
While stress has been found to inhibit adult neurogenesis in the hippocampus – a brain area that is central to emotion, memory and learning –, antidepressant treatment has the opposite effect. Moreover, patients with mood disorders often have reduced hippocampal volumes. This evidence rapidly led to the formulation of the 'neurogenesis hypothesis' of depression, which says that adult neurogenesis in the hippocampus is a candidate substrate for both the etiology and the treatment of major depressive disorders. However, according to the current view, newborn cells in the hippocampus per se may not be critical for the development of depression, but may be required for certain behavioural effects of antidepressants (Sahay & Hen, 2007).
Recent research has proven that the adult brain is capable of generating new nerve cells (neurons). Neurogenesis can be influenced by positive and negative modulators.
The role of gliogenesis
There is increasing evidence that in addition to neurogenesis, stress and antidepressant treatment also induce changes in the formation of specific glial support cells (=gliogenesis) that are critical for the survival of the neurons in the brain. There are about 100 times more glial cells than nerve cells, providing energy and nutrition to the neurons. Besides their ´housekeeping´ functions, glial cells are instrumental to neural communication and regarded as dynamic regulators of synaptic strength and synapse formation. They also possess receptors for neurotransmitters and steroid hormones that, similarly to receptors of neurons, can trigger electrical and biochemical events in the cell. Therefore, structural changes of glial cells are likely to have an important functional significance for the communication between neurons and between neurons and glial cells.
In the adult brain various antidepressant treatment strategies can not only stimulate neurogenesis, but also exert similar stimulatory effects on gliogenesis. Moreover, animal studies have recently shown that chronic stress inhibits cell proliferation not only in the hippocampus but also in the prefrontal cortex, and that this inhibitory effect can be counteracted by antidepressant treatment (Czéh et al., 2007). The significance of these observations is strengthened by in vivo neuroimaging studies in patients with mood disorders that consistently point to the involvement of prefrontal brain sites in the pathophysiology of the disease. These imaging findings are further supported by reports on human post-mortem tissues revealing that the number of glial cells in the prefrontal cortex is adversely affected in patients with mood disorders.
Experiments show that stress and depression inhibit the growth of new nerve cells as well as glial support cells, and that this inhibitory effect can be counteracted by antidepressive therapy.
Clinical implications
Within the last two decades, the understanding of the mature brain has changed: Neuronal and glial cell networks in the brain are far from being fixed and immutable – a multitude of factors such as environmental stimulation, learning, growth factors, glucocorticoids, sexual hormones, stress, aging, and several neurotransmitters regulate the generation of new neurons. Antidepressants stimulate the growth of neurons and glial cells again so the brain changes that occur as a consequence of stress and depression are generally reversible.
Today it is widely believed that neurogenesis in the adult brain is restricted to selected brain regions such as zones of the hippocampus and the lateral brain ventricles. However, a growing number of recent studies describe the generation of new neurons also in the adult neocortex. Although small in both number and size, these new cells could have a significant impact on neocortical function.
Interrelation between psychiatric diseases and adult neocortical cytogenesis is suggested by preclinical studies of stress (inhibiting cytogenesis) and antidepressive treatment (stimulating cytogenesis), but so far the existence of a causative relationship remains speculative. Nevertheless these findings should encourage further studies on neocortical cytogenesis and its function in affective disorders such as depression, which may provide additional evidence that impairments of brain neuroplasticity are important features of depressive disorders.
On the basis of this research it might be possible to develop new strategies for more effective therapies of depressive diseases.
These discoveries show that brain cells can be adversely affected by stress and depression which may lead to a new approach to antidepressant treatment.
###
References
Wittchen HU, Höfler M, Meister W. Depressionen in der Allgemeinpraxis. Die bundesweite Depressionsstudie. Stuttgart: Schattauer, 2000
Moussavi S, Chatterji S, Verdes E, et al. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 2007;370:851-858
World Health Organisation (WHO). The World Health Report 2001. Mental Health: New Understanding, New Hope. Download http://www.who.int/whr/2001/en/whr01_en.pdf
Sahay A, Hen R. Adult hippocampal neurogenesis in depression. Nature Neuroscience 2007;10:1110-1115
Ramón y Cajal, SR. Degeneration and regeneration of the nervous system. London, Oxford University Press, 1928
Czéh B, Müller-Keuker JIH, Rygula R, et al. Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment. Neuropsychopharmacology 2007;32:1490-1503
Correspondence: Professor Eberhard Fuchs, Dr. rer. nat. Clinical Neurobiology Laboratory, German Primate Center, Goettingen, and Department of Neurology, University Medical Center, Georg-August-University Goettingen, Germany E-mail: efuchs@gwdg.de