Saturday, November 24, 2012

60% Of Largest U.S. Cities Now Have Smoke-Free Laws

Out of the 50 largest cities in America, 30 are now protected by smoke free laws which ban smoking from all indoor parts of bars, restaurants and private work areas, according to a recent report released by the CDC (Centers for Disease Control and Prevention).

The report states that at the end of 2000, only one of these 50 cities had these types of laws, and by October 5, 2012, 16 were protected with local comprehensive smoking laws, while 14 had state comprehensive laws.

A study published in August of this year said that although smoking rates have dropped, other types of tobacco usage has increased.

In 2000, only about 3% of American were covered by smoke-free laws, now, almost 50% of Americans live smoke-free because of these local and state laws. Previous studies have revealed that smoke-free laws dramatically help lower exposure to secondhand smoke and improve health among the public. For example, the laws have helped reduce heart attack rates. For the first time since 2012, last week, the people of North Dakota voted to approve a comprehensive smoke-free law statewide.

CDC Director Thomas R. Frieden, M.D., M.P.H, commented:

"Communities have made tremendous progress eliminating smoking from worksites and public places in 60 percent of big cities in the United State. Smoke-free laws save lives and don't hurt business. If we can protect workers and the public in the remaining 20 largest cities, 16 million people would be better protected from cancer and heart disease caused by secondhand smoke."

The recent trial, tittled "Comprehensive Smoke-Free Laws - 50 Largest U.S. Cities, 2000 and 2012" was published in the CDC's Morbidity and Mortality Weekly Report this week and stated that out of the 20 cities that do not have comprehensive smoke-free laws, 10 are southern cities. Also, 10 of the 20 cities that do not currently have the laws are found in states that do not allow smoking bans to be considered more important than any other law.

Tim McAfee, M.D., M.P.H., director of the CDC's Office on Smoking and Health, added:

"Hundreds of cities and countries have passed their own smoke-free laws, including many communities in the south. If we continue to progress as we have since 2000, all Americans could be protected from secondhand smoke exposure in workplaces and public places by 2020."

The 2006 Surgeon General's Report notes that secondhand smoke is always dangerous; it results in the development of heart disease and lung cancer in people who don't even smoke themselves. In addition, secondhand smoke can cause SIDS (sudden infant death syndrome), asthma, ear infections, and respiratory problems in babies and children.

Cigarette smoke kills around 443,000 Americans every year, 46,000 from heart disease and 3,400 by lung cancer in people who do not smoke, solely due to secondhand smoke exposure.
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New Respiratory Coronavirus Claims Second Victim

Another person with a severe acute respiratory infection (SARI) caused by a novel coronavirus 2012 has died, the World Health Organization (WHO) announced on Friday. The second victim, like the first, died in Saudi Arabia.

The announcement follows enhanced surveillance in Saudi Arabia and Qatar that has identified 4 new cases (3 in Saudi Arabia, 1 in Qatar), including the second death, the United Nations health agency reports.

Human coronoviruses are so called because of the crown-like projections on their surfaces. First identified in the 1960s, they are a large family of viruses that cause illnesses in animals and humans.

The illnesses they cause include respiratory infections such as the common cold and SARS (severe acute respiratory syndrome). In 2002, an oubreak of SARS spread from Hong Kong around the world, killing around 800 people.

However, according to information published on the WHO website at the end of September, the new coronavirus is genetically quite distinct from SARS.

The WHO says globally, the total of lab-confirmed cases of novel coronavirus 2012 notified to them is now 6, with 4 of them (including 2 deaths) linked to Saudi Arabia and 2 to Qatar (one reported from the UK and the other from Germany).

Two of the recently confirmed cases in Saudi Arabia are "epidemiologically linked" and from the same family and household. One person died and the other has since recovered, says the WHO.

Two other family members have also been tested: so far one is negative and the result of the other is not yet available.

According to the UK's Health Protection Agency (HPA), the newly reported case from Qatar, was lab-confirmed by them in November. The patient was initially treated in Qatar in October, but then transferred to Germany, and has now been discharged.

The WHO is now reviewing these new developments to see if there is a need to revise the interim case definition it published at the end of September, and any guidance relating to it.

The UN agency says in the meantime:

"Investigations are ongoing in areas of epidemiology, clinical management, and virology, to look into the likely source of infection, the route of exposure, and the possibility of human-to-human transmission of the virus. Close contacts of the recently confirmed cases are being identified and followed up."

The international agency says there is a need for more studies to better understand the virus, and encourages all members of the UN to continue their surveillance of severe acute respiratory infections (SARI).

It is likely the virus is present in more than just two countries, says the WHO, and it suggests patients with unexplained pneumonias should be tested for the new coronavirus, even if they have not been travelling to the two affected countries or are otherwise associated with them.

"In addition, any clusters of SARI or SARI in health care workers should be thoroughly investigated regardless of where in the world they occur," it urges.

More information from the WHO on coronavirus infections.
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Positive View On Aging May Help Recovery From Severe Disability

New research from the US finds that older people who have a positive view on aging are more likely to recover from severe disability than those who hold negative stereotypes about being older. It calls for more studies to investigate whether promoting positive age stereotypes extends independent living later in life.

Reporting in JAMA this week, the researchers, from Yale School of Public Health, say their study is the first to examine the link between positive age stereotypes and recovery from disability in older persons.

Lead author Becca R. Levy is associate professor of epidemiology (chronic diseases) and of psychology, and is also director of the School's division of social and behavioral sciences. She tells the press in a statement that the findings suggest "how the old view their aging process could have an effect on how they experience it".

"In previous studies, we have found that older individuals with positive age stereotypes tend to show lower cardiovascular response to stress and they tend to engage in healthier activities, which may help to explain our current findings," she adds.

She and her colleagues explain in their background information how few studies have looked at why some older people recover from disability and others do not.

"We considered a new culture-based explanatory factor: age stereotypes (defined as beliefs about old people as a category)," they write.

For their study, they compared participants with different views of aging, categorizing them as having either a positive stereotype or a negative stereotype. Altogether there were 598 individuals, all at least aged 70, and free of disability at the start of the study, which covered about 11 years. They were members of a health plan in greater New Haven, Connecticut.

From March 1998 to December 2008, the participants were interviewed monthly, and they also underwent home-based assessment every 18 months.

The researchers based their measure of recovery on participants being able to carry out four activities of daily living (ADLs): bathing, dressing, moving from a chair, and walking. Doing well in these activities is linked to lower use of healthcare and longevity.

They assessed age stereotypes from responses to the question, "when you think of old persons, what are the first 5 words or phrases that come to mind?"

They scored the responses from 1 for the most negative (eg "decrepit"), to 5 for the most positive (eg "spry") and then averaged them.

The researchers found participants with a positive age stereotype were 44% more likely to fully recover from severe disability than those with a negative age stereotype.

Those with a positive view on aging also showed a significantly lower rate of decline in ability to perform their daily tasks.

The researchers suggest:

"Positive age stereotypes may promote recovery from disability through several pathways: limiting cardiovascular response to stress, improving physical balance, enhancing self-efficacy, and increasing engagement in healthy behaviors."

"Further research is needed to determine whether interventions to promote positive age stereotypes could extend independent living in later life," they urge.
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Revolutionary Stem Cell Treatment Repairs Spinal Cord Injuries In Paralyzed Dogs

Scientists have used a special cell to regenerate damaged parts of dogs' spines. Researchers are cautiously excited about these results which could potentially have a future role in the treatment of human patients with similar spinal injuries.

For many years, scientists have been aware that olfactory ensheathing cells (OEC) could be helpful in treating the damaged spinal cord because of their distinctive properties. The unique cells have the capacity to support nerve fiber growth that preserves a pathway between the nose and the brain.

Earlier studies consisting of laboratory animals have shown that OECs can be helpful in regeneration of the parts of nerve cells that pass on signals (axons). OECs were used as a bridge linking damaged and undamaged tissues in the spinal cord. A Phase 1 trial in humans with spinal cord injuries has determined that the procedure is safe.

The current study, published in the journal Brain, is the first double-blinded, randomized, controlled study to examine the effectiveness of these transplants to increase function in spinal cord injuries. The trial used animals with spontaneous and accidental spinal cord injuries. This method resembled closely the way the procedure could potentially work for human patients.

The study included 34 dogs that all suffered critical spinal cord injuries (SCIs). A year or more after the injury, the dogs were without the ability to use their legs and were unable to feel pain in their hind legs and adjoining areas.

Stem cell image
Researchers say that paralysis was reversed in Jasper the dachshund using cells grown from the lining of his nose.
Several of the dogs were dachshunds, who are extremely prone to this type of injury. Dogs in general are more likely to experience SCIs because they can be caused by a slipped disc, which is normally a minor injury in humans.

One group involved in the study received OECs from the lining of their own nose injected into the injured area. The other group of dogs were injected with only the liquid in which the cells were transplanted. The researchers and the owners were both in the dark about which dogs received which type of injections.

The dogs were analyzed for adverse reactions during a 24 hour period before being returned to their owners. After that, they were tested every month for neurological function and to have their walking manner assessed on a treadmill while being supported in a harness. Specifically, the researchers watched to see if the dogs could coordinate the movement of their front and back legs.

The groups of dogs that received the OEC injection had significant improvement that was not present in the other group. The OEC injection group was able to move previously paralyzed legs and coordinate these movements with their front quarters.

This suggests that in these particular dogs, neuronal messages were being relayed across the formerly damaged part of the spinal cord. The researchers found that the new nerve connections causing this recovery were happening over short distances within the spinal cord and not among long distances needing the brain to connect with the spinal cord.

Professor Robin Franklin, a co-author of the study from the Welcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, said:

"Our findings are extremely exciting because they show for the first time that transplanting these types of cell into a severely damaged spinal cord can bring about significant improvement.

We're confident that the technique might be able to restore at least a small amount of movement in human patients with spinal cord injuries but that's a long way from saying they might be able to regain all lost function. It's more likely that this procedure might one day be used as part of a combination of treatments, alongside drug and physical therapies, for example."

The authors emphasize that human patients with a spinal cord injury rate a restoration in sexual function and continence much greater than better mobility. Some dogs in the study got back their bowel and bladder control but the number was not satistically exceptional.

Dr Rob Buckle, Head of Regenerative Medicine at the MRC, commented:

"This proof of concept study on pet dogs with the type of injury sustained by human spinal patients is tremendously important and an excellent basis for further research in an area where options for treatment are extremely limited. It's a great example of collaboration between veterinary and regenerative medicine researchers that has had an excellent outcome for the pet participants and potentially for human patients."
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Prescription Drug Addiction Is Now An Epidemic

The abuse of prescription drugs is currently an epidemic because doctors are treating pain differently now than in past years.

Drug abuse was recently referred to as an "epidemic" in a newspaper article by a Nebraska State Patrol investigator. "Clinically, it's a very common problem," added Aly Hassan, M.D., assistant professor of psychiatry in the University of Nebraska Medical Center College of Medicine.

The '90s were considered to be the decade of treatment of pain, the Dr. explained. Not only was there a change in medication, but there was also a change in policy.

"An important aspect of that was to consider pain as the fifth vital sign," he said. The other four vital signs are:
  • pulse rate
  • body temperature
  • blood pressure
  • respiratory rate
Doctors' offices frequently have signs hanging that ask patients to rank their pain on a scale from 1 to 10. According to Dr. Hassan, this is not because people these days are weaker and can not handle the pain, it is because pain is very serious and people need to receive the proper treatment.

"The experience of pain is not only somatic. It's not just the nerve being stimulated," Dr. Hassan said. A patient's vital signs are impacted by acute pain, causing a change in the person's quality of health. However, with treatment, the vital signs become normalized.

For that reason, doctors began to emphasize the importance of treating pain, but that meant more drugs.

The drug prescribed the most in 2011 was hydrocodone, according to WebMD. However, the medical field was not too concerned about people becoming addicted to their prescribed drugs, at least at first.

"The pain patient can be treated with narcotics with little risk of developing the self-destructive behavior characteristic of addiction," stated a 1990 report: "The Use of Narcotics for the Treatment of Chronic Pain," by the Sacramento-El Dorado Medical Society.

In 2012, Dr. Hassan pointed out that several of these drugs have similar characteristics to other addictive drugs:
  • absorb quickly
  • the half-like of the medicine staying in your system goes very fast
"The opiates are very addictive for that reason," Dr. Hassan said, because it makes a person want to take another one.

This puts clinicians in a bad situation because it is their job to prescribe these potentially addictive drugs. "This is beyond the level of an individual practitioner," Dr. Hassan said. "This is really a state problem or even a national problem."
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Heart Attack Risk Higher With Job Loss

New research on older adults in the US finds that being unemployed, experiencing multiple job loss and even going for short periods without work is tied to a greater risk for heart attack (acute myocardial infarction, AMI) compared with no job loss. The researchers suggest people who suffer multiple job losses have a risk for heart attack that is on a par with smoking.

Matthew E. Dupre and colleagues from Duke University, Durham, North Carolina, write about their findings in the November 2012 online first issue of JAMA's Archives of Internal Medicine.

There is lots of evidence that unemployment is a major source of strain, something that is affecting a growing number of adult Americans. However, there is little research on how the build up of multiple job loss and being out of work affects the risk of having a heart attack (AMI).

The Study

For their analysis, Dupre and colleagues looked at the links between aspects of unemployment and the risk for AMI in 13,451 adult Americans aged between 51 and 75 years who took part in the Health and Retirement Study, where participants underwent follow up interviews every two years between 1992 and 2010.

They found several aspects of past and present employment status raised the risk for a cardiovascular event, and:

"Although the risks for AMI were most significant in the first year after job loss, unemployment status, cumulative number of job losses and cumulative time unemployed were each independently associated with increased risk for AMI," they write.

The median age of the group was 62, and over the whole follow up period the data covered 165,169 person-years of observation, during which 1,061 (7.9%) of the participants reported having a heart attack.

At the start of the study period, 14% of the participants were out of work, 69.7% had one or more cumulative job losses, and 35.1% reported having spent some time out of work.

Using statistical tools to calculate hazard ratios, the researchers worked out that risk for heart attack was a significant 35% higher among the unemployed compared to those who had not experienced job loss.

On a Par with Smoking, Other Hazards

The more jobs people lost, the higher their risk for heart attack, the researchers found (22% for one job loss, rising to 63% for those who had lost four or more jobs).

And the risk of having a heart attack was "particularly elevated" during the first twelve months of unemployment (27% higher risk), but not after that, they write.

They also note that the higher risk for heart attack linked to multiple job loss is on a par with other more traditional risk factors, such as smoking, type 2 diabetes and high blood pressure.

New Era of Looking at Job Loss and Health

The researchers call for further studies to look more closely at how work-related disparities in the population could be affecting risk for heart attack so as to identify targets for health initiatives.

They say this is especially important, given the current economic climate and the projected increases in job instability and unemployment in the US.

In an accompanying commentary, William T. Gallo of the City University of New York, says the study marks the start of a new era where we look more closely at how changes in socioeconomic factors like job loss affect heath.

"Sufficient evidence exists of the negative influence of job loss on health. The next generation of studies should identify reasonable pathways from job separation to illness so that nonoccupational interventions may be developed and targeted to the most vulnerable individuals," he adds.
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Diabetes Rises "Dramatic", CDC Report

Over the past decade and a half, the United States has seen a "dramatic" rise in rates of diagnosed diabetes, according to a study from the Centers for Disease Control and Prevention (CDC). The study editors suggest the rise is likely due to people with diabetes living longer as well as increases in diabetes cases.

A report on the study is published in the 16 November issue of the CDC's Morbidity and Mortality Weekly Report (MMWR).

Diabetes Rises Across the US

The report shows that between 1995 and 2000 the prevalence of diagnosed diabetes in all states of the US, plus the District of Columbia and Puerto Rico, increased by 50% or more in 42 states, and by 100% in 18 states.

Ann Albright, director of CDC's Division of Diabetes Translation, says in a press statement that in 1995, there were only three states, the District of Columbia and Puerto Rico, where 6 out of 100 people or more had been diagnosed with diabetes.

"By 2010, all 50 states had a prevalence of more than 6%", she adds.

By region, the largest increases are in the South, followed by the West, Midwest and Northeast, says report first author Linda Geiss.

The states showing the largest increases are Oklahoma (226%), Kentucky (158%), Georgia (145%), Alabama (140%), and Washington (135%).

The report shows that in 2010, six states plus Puerto Rico have a diagnosed diabetes rate of at least 10 adults in 100. The six states, all in the South and Appalachia, are Alabama, Mississippi, South Carolina, Tennessee, Texas and West Virginia.

"These data also reinforce findings from previous studies, which indicate that the prevalence of diagnosed diabetes is highest in the southern and Appalachian states," adds Geiss.

The states with the lowest diabetes rates in 2010, that is between 6.0 and 6.9%, are Alaska, Colorado, Connecticut, Iowa, Minnesota, Montana, North Dakota, Oregon, South Dakota, Wisconsin, Vermont and Wyoming.

Telephone Survey

Geiss and colleagues analyzed data from the Behavioral Risk Factor Surveillance System, an annual telephone survey that asks adults (people aged 18 and over) across the US a range of questions about their health.

The survey asks people whether a doctor has ever told them they have diabetes, and while it does not distinguish between type 1 and type 2 diabetes, it is known that 90 to 95% of diabetes patients in the US have type 2, which can be prevented through lifestyle changes.

The figures exclude women told that they had diabetes only during pregnancy, and people told they had prediabetes or borderline diabetes.

Obesity Highlighted as a Driver of Diabetes

The report editors suggest the main driver of these increases is the rise in incidence of diabetes in the US since 1990. This could be as a result of many things, including changes in how the disease is diagnosed, improved ways of detecting it, changes in the population (for instance more older people and minorities who have an increased risk for the disease), and a rise in the risk factors, such as obesity and sedentary lifestyles.

"Although the contribution of each factor to increasing diabetes incidence cannot be discerned, the increase in diabetes prevalence coincides with the increase in obesity prevalence across the United States," they note.

Albright says:

"These rates will continue to increase until effective interventions and policies are implemented to prevent both diabetes and obesity."

CDC Initiatives

The CDC says it is working with a number of partners to offer ways to prevent type 2 diabetes and reduce complications in people who have already been diagnosed with the disease.

One of these is the National Diabetes Prevention Program, that helps people change their lifestyle to reduce risk of developing type 2 diabetes. This is done through a network of classes aimed particularly at obese and overweight people.

Another initiative is the National Diabetes Education Program, which provides resources to prevent or delay the onset of type 2 diabetes, promote early diagnosis, and improve the treatment and outcomes for patients.

And the latest initiative, whose launch coincides with this report, is the Diabetes Interactive Atlases, "which provides data for diagnosed diabetes, obesity and leisure-time physical inactivity at the national, state and county levels".

The Interactive Atlases also include motion charts showing trends in the growth of diabetes and obesity across the US and within its states.
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Nanoparticles Stop Multiple Sclerosis In Mice

A breakthrough new experimental treatment that uses nanoparticles covered with proteins to trick the immune system, managed to stop it attacking myelin and halt disease progression in mice with relapsing remitting multiple sclerosis (MS). The researchers say the approach may also be applicable to other auto-immune diseases such as asthma and type 1 diabetes.

Corresponding author Stephen Miller is the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine in Chicago in the US. He says in a statement:

"We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks."

"We prevented any future relapses for up to 100 days, which is the equivalent of several years in the life of an MS patient," he adds.

The study results suggest the nanoparticles are as effective as using patients' own white blood cells to deliver the antigen, an approach that is being tested in a phase I/II trial in MS patients. Using nanoparticles would be much cheaper and easier, say the researchers.

Miller and colleagues report their study, which was funded by the Myelin Repair Foundation, the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIH), and the Juvenile Diabetes Research Foundation, in the 18 November online issue of Nature Biotechnology.

Multiple Sclerosis (MS)

An auto-immune disease is where the immune system mistakenly attacks healthy tissue as well as clearing away harmful pathogens and cell debris. The type of tissue it attacks gives rise to different diseases.

In the case of Multiple Sclerosis (MS), the auto-immune target is myelin, the protein that forms the protective sheath that insulates nerve fibers in the brain, spinal cord and eyes and preserves the vital electrical signals they carry.

When the myelin is destroyed, the electrical signals can't travel, and the result is the characteristic symptoms of MS, which range from mild limb numbness to paralysis or blindness.

About 80% of MS patients have the relapsing remitting form of the disease, where there are periods of symptom flare-up (relapse) interspersed with periods where they stop (remit), either partially or completely.

Protein-Covered Biodegradable Nanoparticles Trick the Immune System

The researchers used biodegradable nanoparticles covered with myelin proteins or antigens to trick the immune system into treating myelin as "friendly". The nanoparticles are made from the same material as dissolvable stitches, except they are much smaller, about 200 times thinner than human hair.

For their study, they injected the nanoparticles, bearing their myelin antigen cargo, into mice bred to develop a disease similar to the human form of relapsing remitting MS.

The particles travelled to the spleen, a key immune system organ that removes unwanted materials such as old and dying cells from the blood, makes new blood cells and stores blood platelets.

Once in the spleen, the particles were engulfed by macrophages, white blood cells that literally gobble up and digest pathogens and unwanted materials and then send signals to other immune cells to target those materials.

But the effect in this case was to make the immune system view the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the myelin antigen by directly inhibiting the myelin responsive T cells. It also increased the numbers of regulatory T cells and further calmed the autoimmune response.

"Resets" Rather than Shuts Down Immune System

An attractive feature of this study is it shows a potential therapy that does not suppress the whole immune system as do current therapies for MS, which make patients more vulnerable to everyday infections and put them at higher risk for cancer.

Instead, the nanoparticles, with their myelin antigens, "reset" the immune system to normal. The result is it stops treating myelin as an alien invader and stops attacking it.

Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the NIH, says:

"The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system."

Biodegradable Material Is Already FDA Approved

The nanoparticles Miller and colleagues used are made of a polymer called Poly(lactide-co-glycolide) (PLG), which comprises lactic acid and glycolic acid, both natural metabolites in the human body. PLG is most commonly used for biodegradable sutures or dissolvable stitches.

Because PLG is already approved by the US Food and Drug Administration (FDA) for other uses, this should make it easier to get approval for using it to move this research from mice to human subjects.

The nanoparticles used in this study were developed by co-corresponding author Lonnie Shea, professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.

The researchers tested different sizes of nanoparticles and found 500 nanometers was the best at resetting the immune response.

Potential for Treating Range of Auto-Immune Diseases

Miller says:

"The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered."

Shea and Miller are currently testing the nanoparticles to treat type 1 diabetes and airway diseases such as asthma.

Nanoparticles offer an attractive alternative to other approaches: they can be readily produced in a laboratory and standardized for manufacturing. This suggests therapies based on these mateials would be cheaper and more accessible to a general population.

Scott Johnson, CEO, president and founder of the Myelin Repair Foundation, says:

"The overarching goal is to ensure this important therapeutic pathway has its best chance to reach patients, with MS and all autoimmune diseases."
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Blood Flow Changes, Not Hormones, Explain Growth Of Benign Tumors In Pregnant Women

Meningiomas are a common type of benign brain tumor that sometimes grows dramatically in pregnant women. A new study suggests that this sudden tumor growth likely results from "hemodynamic changes" associated with pregnancy, reports the November issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The study also identifies some key characteristics associated with rapid growth of meningiomas in pregnant women. The lead author was Dr. Eriks A. Lusis of Washington University School of Medicine, St Louis, Mo.

'Dramatic Growth' of Meningiomas in Pregnant Women

From the records of four university medical centers, the researchers identified 17 women with meningiomas requiring surgery during pregnancy, or shortly afterward. Meningiomas are relatively common, usually benign (noncancerous) tumors that arise in the tissues lining the brain (meninges). They cause problems when they grow large enough to affect brain functions.

Over the years, there have been several reports of meningiomas enlarging or becoming symptomatic during pregnancy. For this reason - and because meningiomas occur more often in women than men - it has sometimes been assumed that rapid tumor growth is related to changes in hormone levels during pregnancy. Dr. Lusis and colleagues sought to evaluate this theory, as well as to look at other characteristics of meningiomas in pregnant women.

Surgery for meningioma was successful in 16 of the 17 patients; the remaining patient died before surgery. Most of the women developed meningioma-related symptoms during the third trimester of pregnancy or within eight days after delivery. The most common symptoms of enlarging meningioma were changes in vision and facial paralysis or other cranial nerve palsies.

Most of the tumors were located in the skull base region and were typical, "low-grade" benign tumors. At surgery, the tumors showed an unusual "hypervascular" pattern, which was not seen in other cases of meningioma in non-pregnant patients. There was also a high rate of edema (swelling) in and around the tumor.

These and other findings strongly suggested that the rapid tumor growth resulted from "potentially reversible hemodynamic changes" - changes in blood flow - related to pregnancy. The pattern did not support the theory that meningioma growth resulted from "hormone-induced cellular proliferation."

The results may help to explain the uncommon but well-documented occurrence of rapid meningioma growth during pregnancy. Since most meningiomas don't cause any symptoms, they may go undetected. Even if they are detected, they may require no treatment unless they grow.

Together with previous evidence, the findings may have implications for the management of meningiomas in women of child-bearing age. Dr. Lusis and coauthors write, "[F]or the vast majority of women of child bearing age, we would not consider the presence of residual or unresected meningioma to be a contraindication to pregnancy." In contrast, for patients with evidence of tumor growth or swelling, the authors suggest they might consider treating the tumor before pregnancy.
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Ribosome Regulates Viral Protein Synthesis, Revealing Potential Therapeutic Target

Viruses can be elusive quarry. RNA viruses are particularly adept at defeating antiviral drugs because they are so inaccurate in making copies of themselves. With at least one error in every genome they copy, viral genomes are moving targets for antiviral drugs, creating resistant mutants as they multiply. In the best-known example of success against retroviruses, it takes multiple-drug cocktails to corner HIV and narrow its escape route.

Rather than target RNA viruses themselves, aiming at the host cells they invade could hold promise, but any such strategy would have to be harmless to the host. Now, a surprising discovery made in ribosomes may point the way to fighting fatal viral infections such as rabies.

Results were published online in Proceedings of the National Academy of Sciences.

The ribosome has traditionally been viewed as the cell's molecular machine, automatically chugging along, synthesizing proteins the cell needs to carry out the functions of life. But Amy Lee, a former graduate student in the program of virology, and Sean Whelan, HMS professor of microbiology and immunobiology, now say the ribosome appears to take a more active role, regulating the translation of specific proteins and ultimately how some viruses replicate.

The researchers were studying differences between how viruses and the host cells they infect carry out the process of translating messenger RNAs (mRNAs) into proteins. Focusing on protein components found on the surface of the ribosome, they discovered a protein that some viruses depend on to make other proteins, but that the vast majority of cellular mRNAs do not need.

Called rpL40, this ribosomal protein could represent a target for potential treatments; blocking it would disable certain viruses while leaving normal cells largely unaffected.

"Because certain viruses are very sensitive to the presence and absence of these ribosomal proteins, it might be a useful way for us to think about targeting ribosomes for therapeutic purposes from an antiviral standpoint," said Whelan. "This is a way to think about interfering with rabies virus infection. There are no therapeutics for rabies infection."

The team screened protein constituents of the ribosome to see which ones might be involved in specialized protein synthesis. Studying the vesicular stomatitis virus, a rhabdovirus in the same family as the rabies virus, they found that its mRNAs depended on rpL40 but only 7 percent of host-cellular mRNAs did. Some of the cellular mRNAs that depend upon rpL40 were stress response genes.

Experiments in yeast and human cells revealed that a class of viruses, which includes rabies and measles, depended on rpL40 for replication.

"This work reveals that the ribosome is not just an automatic molecular machine but instead also acts as a translational regulator," said first author Amy Lee, who is now a post-doctoral researcher at the University of California, Berkeley.

The concept of targeting cellular functions such as protein synthesis for antiviral therapies is being explored by a number of research groups, but there are no drugs based on this.

"We think the principle is bigger than just this single protein," Whelan said. "Viruses have an uncanny way of teaching us new biology all the time."
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Decline In Availability And Use Of ECT, A Key Treatment For Depression

Electroconvulsive therapy (ECT) is considered the most effective treatment option for patients with severe depression who cannot find symptom relief through antidepressant medications or psychotherapy. In a new study, researchers at Butler Hospital and Bradley Hospital in Rhode Island found a sharp decline in the availability and use of ECT in general hospitals across the U.S. The findings were published online in the journal Biological Psychiatry.

The researchers analyzed data from a nationally representative survey of US general hospitals, the Nationwide Inpatient Sample (NIS), conducted annually by the Agency for Healthcare Research and Quality (AHRQ). They took information from between five and eight million patient discharge records at 1,000 hospitals nationwide between the years 1993 through 2009 and found that the annual number of hospital stays in which ECT was administered fell 43 percent over the 17 year period, from more than 1.2 million to 720,000. Researchers also found a dramatic decline in the percentage of hospitals conducting ECT, from 55 percent to 35 percent of facilities with a psychiatric unit. The percentage of inpatients with severe, recurrent major depression treated in hospitals conducting ECT fell from 71 to 45 percent. But for depressed patients treated in hospitals that conduct ECT, the proportion who received the procedure remained stable.

"The data strongly support the impression that psychiatric units in general hospitals are discontinuing use of ECT and that this is driving the decline in the number of severely depressed inpatients receiving the procedure," said Brady Case, MD, an assistant professor of psychiatry and human behavior at Brown University and director of the Health Services Research Program at Bradley Hospital. "Growing pressures to avoid the inpatient treatment costs and length of stay associated with ECT may be one factor associated with this trend. We didn't have information on provider and patient attitudes, but as facilities cease conducting ECT, we can expect that fewer clinicians and inpatients are exposed to the option, reinforcing the turn away from ECT." Researchers also note the FDA approval of new treatment alternatives, like vagus nerve stimulation and transcranial magnetic stimulation, as possible influences.

Declines in ECT availability and use were particularly dramatic in elderly patients, a group traditionally thought to benefit most from the procedure. "Decreased availability of ECT for older patients with severe depression is of major concern, since a significant proportion of this group fails to benefit from available medication treatments. In such cases, ECT can literally be a life-saving intervention," said Lawrence Price, MD, clinical and research director at Butler Hospital and professor of psychiatry and human behavior at Brown University.

The researchers also noted a key finding they observed throughout the 15-year study period: depressed inpatients from poor neighborhoods and those who were publicly insured or uninsured were less likely to receive care from hospitals conducting ECT. "Access to ECT for less affluent patients has concerned the field for some time, but these data really drive home the reality. The worry is that ECT may be part of a tiered system of psychiatric care that deprives the disadvantaged of one of our most effective treatments," according to Price.

The researchers acknowledge that a limitation of the study is its exclusion of data from freestanding psychiatric facilities. Case and his colleagues note that psychiatric hospitals less commonly offer ECT than general hospitals, possibly because the procedure requires a level of medical support more readily available in general hospitals. Because of this, and the fact that psychiatric hospitals have accounted for a declining proportion of inpatient mental health care, the researchers argue that this exclusion is unlikely to have offset the declines they observed.

The data also do not include information on outpatient ECT, but many severely ill patients are inappropriate for outpatient ECT initiation. Case concedes that while "changing pharmacologic treatment practices for depression have received an immense amount of attention, we still know very little about how and where ECT is being used, especially outside of academic medical centers."
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Simple, Inexpensive Way To Improve Healing After Massive Bone Loss Could Help With Battlefield Injuries

Bones are resilient and heal well after most fractures. But in cases of traumatic injury, in which big pieces of bone are missing, healing is much more difficult, if not impossible. These so-called "large segmental defects" are a major clinical problem, and orthopaedic surgeons struggle to treat them, especially among the military in places like Afghanistan.

Now research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) offers surgeons a new approach. Described on-line in today's issue of the Journal of Bone and Joint Surgery, the results confirm that the bone healing process of large segmental defects is exquisitely sensitive to its mechanical environment and suggests that "reverse dynamization," a straightforward and inexpensive process, could help speed healing of these traumatic injuries.

"Bones are greatly influenced by their mechanical environment, which is why casts, rods, plates and screws are typically used to heal fractures - with a great deal of success," explains senior author Christopher Evans PhD, Director of the Center for Advanced Orthopaedic Studies at BIDMC. "But until now, no one has examined the relevance of the mechanical environment to the healing of large segmental bone defects."

According to the American Association of Orthopaedic Surgeons (AAOS), these injuries are one of the most demanding surgical challenges faced by orthopaedic trauma surgeons. Often as large as 20 centimeters in length, large segmental defects can be complicated by regional soft-tissue loss, reduced vascularity, regional scarring and infection. The AAOS notes that an increased number of missions being conducted on foot in Afghanistan has led to an increase in this type of combat blast injury.

Changing levels of stiffness during bone healing is known as "dynamization." During standard dynamization, bone is first held rigidly in place by a mechanical intervention, or fixation device. Once healing has begun, the stiff rigidity is loosened to allow movement. "An 'external fixator' is placed on the outside of the skin and usually has a 'cross-bar' that determines the level of rigidity and can be adjusted to allow more or less motion," explains Evans, who is also the Maurice Edmond Mueller Professor of Orthopaedic Surgery at Harvard Medical School. Evans and his colleagues thought that how firmly or loosely injured bone is held together by mechanical interventions - casts, rods, plates and screws - could impact these large segmental bone defects, just as it does for more minor fractures - but with one big difference. The scientists changed stiffness levels in the opposite order - hence, "reverse dynamization."

"Our laboratory has a lot of experience with a rat model of segmental defect healing, and we noticed that during the healing process, the defect first fills with cartilage, and then the cartilage turns to bone," says Evans. Technically known as "endochondral ossification" this process is well documented to occur in fracture healing. 'We knew from other previous work that the early formation of cartilage is helped when mechanical fixation is loose. We also knew that a subsequent increase in fixator stiffness would provide the rigidity needed for the ingrowth of blood vessels and other aspects of healing." Evans and his coauthors hypothesized that a period of loose "fixation" followed by a period of stiffened "fixation" would accelerate healing of large segmental defects. "If bones are allowed to move slightly, cartilage will form in the defect," he adds. "If the area is then held rigidly in place, the new cartilage will then turn to bone."

The team constructed external fixators capable of providing varying degrees of stiffness during the healing process. By implanting a growth factor called bone morphogenetic protein-2 on a collagen sponge, the scientists initiated healing of segmental defects in the femurs of 60 rats. Groups of the animals were then allowed to heal with either low-, medium-, or high-stiffness fixators. Healing also took place under conditions of reverse dynamization, in which the stiffness levels were changed from low to high after a period of two weeks. After eight weeks, the researchers assessed healing using various measures including radiographs, microscopic analyses, and mechanical tests.

The investigators found that when they looked only at unchanging stiffness, the low-stiffness fixator produced the best healing; however, by comparison, the reverse dynamization provided considerable improvement, leading to a marked acceleration in the healing process by all tests. Also, notes Evans, the bone mineral content and bone area of the defects healed by reverse dynamization were closer to normal, and the healed bone had greater mechanical strength.

"Our study confirms the exquisite sensitivity of bone healing to its mechanical environment," he notes. The next step, says Evans, will be to see if this therapy works in large animals, while also gathering more information about the biological mechanisms that are at play. But, he adds, moving these findings into a clinical setting should be relatively straightforward. "The nice thing about this approach is that it's simple and could be rapidly translated to human use if our proposed large-animal studies are successful. The regulatory hurdles should be minor." Furthermore, he adds, reverse dynamization might also be applicable to other situations for which bone healing is problematic. "Sometimes in smokers or individuals with diabetes, fractures heal poorly," he notes, adding that the same can be true when an infection is present.

Reverse dynamization is also an attractive option in terms of cost. "Often, strategies devised in the lab to solve clinical problems are far too complex and expensive to be translated into meaningful clinical use," notes study coauthor Mark Vrahas, MD, Chief of the Harvard Orthopaedic Trauma Service. "But if the promise of this strategy holds out, it will be inexpensive enough to be used even in developing countries, where the burden of severe injuries are particularly high."
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Friday, November 9, 2012

Colon Cancer Patients Who Consume Too Much Starchy, High Carbohydrate Food At Greater Risk For Cancer Recurrence

Colon cancer survivors whose diet is heavy in complex sugars and carbohydrate-rich foods are far more likely to have a recurrence of the disease than are patients who eat a better balance of foods, a new study by Dana-Farber Cancer Institute researchers indicates.

The connection is especially strong in patients who are overweight or obese, the authors write. More than 1,000 patients with advanced (stage III) colon cancer participated in the study, one of the first to examine how diet can affect the chances that the disease will recur. The findings are published online by the Journal of the National Cancer Institute and will appear later in the journal's print edition.

Although the results point to a potential hazard, for colon cancer patients, of a high-carbohydrate diet, the take-home message is not a conclusive "Eat less sugar," said lead author Jeffrey Meyerhardt, MD, MPH. "Our study certainly supports the idea that diet can impact the progression of colon cancer, and that patients and their doctors should consider this when making post-treatment plans. But further research is needed to confirm our findings."

Recent studies have shown that colorectal cancer survivors whose diet and activity patterns lead to excess amounts of insulin in the blood have a higher risk of cancer recurrence and death from the disease. High insulin levels can be produced by eating too many starchy and sugar-laden foods. In a previous study of advanced-stage colon cancer patients, Meyerhardt and his colleagues found that those with a typical "Western" diet -- marked by high intakes of meat, fat, refined grains, and sugar desserts -- were three times more likely to have a cancer recurrence than those whose diets were least Western. The new study was conducted to explore which component of the Western diet is most responsible for the increased risk of recurrence.

The study involved 1,011 stage III colon cancer patients who had undergone surgery and participated in a National Cancer Institute-sponsored Cancer and Leukemia Group B clinical trial of follow-up chemotherapy for their disease. Participants reported their dietary intake during and six months after the trial.

Researchers tracked the patients' total carbohydrates, as well as their glycemic index (a measure of how quickly blood sugar levels rise after eating a particular food), and glycemic load (which takes into account the amount of a carbohydrate actually consumed), and looked for a statistical connection between these measures and the recurrence of colon cancer.

They found that participants with the highest dietary levels of glycemic load and carbohydrate intake had an 80 percent increased risk of colon cancer recurrence or death compared with those who had the lowest levels. Among patients who were overweight or obese (had a body mass index above 25 kg/m2), the increase was even greater.

"In light of our and other's research, we theorize that factors including a high glycemic load may stimulate the body's production of insulin," Meyerhardt said. "That, in turn, may increase the proliferation of cells and prevent the natural cell-death process in cancer cells that have metastasized from their original site."

Meyerhardt added that while the study doesn't prove that diets high in glycemic load and carbohydrate intake cause recurrence of colon cancer, the results strongly suggest that such dietary factors play a role. "Our findings may offer useful guidance for patients and physicians in ways of improving patient survival after treatment."
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In Xenograft Model, Spread Of Human Melanoma Cells Correlates With Clinical Outcomes In Patients

UT Southwestern Medical Center scientists led by Dr. Sean Morrison, director of the Children's Medical Center Research Institute at UT Southwestern, have developed an innovative model for predicting the progression of skin cancer in patients.

In a new study published in Science Translational Medicine, Stage III human melanoma cells from 20 patients were implanted into specially selected mice with compromised immune systems. Using this xenograft model, in which tissue is transplanted from one species to another, the institute's team observed reproducible differences in the rate at which the cancer spread in the mice, or metastasized, that correlated with clinical outcomes in patients.

Dr. Morrison said human melanomas that metastasized efficiently in the mice eventually progressed to advanced, Stage IV disease in patients - spreading to distant organs, such as the brain, liver, or lungs. When the melanoma did not metastasize efficiently in the mice, it also did not form distant metastases in patients.

This xenograft model will make it possible to study the mechanisms that regulate disease progression and distant metastasis of melanomas in patients. The researchers said they hope that their system will lead to new prognostic markers that identify patients at highest risk of disease progression as well as new therapies.

"We believe this is the only time in cancer biology that anyone has developed a xenograft model in which disease progression correlates with what happens in the patient," said Dr. Morrison, senior author of the investigation and a Howard Hughes Medical Institute investigator at UT Southwestern. "The highly immune-compromised state of the mice makes it possible to observe the metastasis of human melanomas, and to study intrinsic differences among melanomas in their metastatic potential."

Previous studies of cancer metastasis were limited by a lack of workable models in which scientists could study the progression of a patient's cancer cells in laboratory animals in a way that correlated with clinical outcomes, he said.

But such correlation was clear in this study by the research institute, an innovative collaboration that melds the leading clinical resources of Children's Medical Center with the outstanding research resources of UT Southwestern. Melanomas that spread slowly and could not be detected in the blood of mice did not form distant tumors within 22 months in patients. Melanomas that spread rapidly in mice did form distant tumors in patients within the same time frame, giving rise to circulating melanoma cells in the blood of the mice. This finding suggests that entry of melanoma cells into the blood is a step that limits the rate of distant metastasis.

"Ultimately we want to identify new drug targets," Dr. Morrison said. "There are promising ideas coming out of this work that we hope will lead to clinical trials in melanoma."

The research arose from the Morrison laboratory's innovative techniques for studying neural crest stem cells - work that was recognized in 2004 with a Presidential Early Career Award for Scientists and Engineers. Neural crest stem cells make melanocytes, a type of cell that can mutate into melanoma if exposed, for example, to excessive sunlight.

The Children's Research Institute focuses on the interface of stem cell biology, cancer, and metabolism and will eventually include approximately 150 scientists in 15 laboratories. The work of Dr. Morrison, who also leads the Hamon Laboratory for Stem Cell and Cancer Biology, focuses on adult stem cell biology and cancers of the blood, nervous system, and skin.

"We're trying to do transformational science that not only changes scientific fields, but also creates new strategies for treating diseases," Dr. Morrison said. "The goal is for our work to have a direct impact on the patient."

Other UTSW researchers involved in the study were Drs. Elena Piskounova and Ugur Eskiocak, both postdoctoral researchers in the Children's Research Institute. This work originated with lead author Dr. Elsa Quintana and Dr. Mark Shackleton in Dr. Morrison's former lab at the University of Michigan. Other key collaborators from the University of Michigan were Dr. Douglas R. Fullen, director of dermatopathology, and Dr. Timothy Johnson, director of the Multidisciplinary Melanoma Clinic.

"This animal model offers unprecedented opportunities for discovery efforts that could be translated into patient care," Dr. Johnson said. "Dr. Morrison and I share a core mission to effectively treat melanoma, and that shared belief is the basis of the past, present, and future collaboration between UT Southwestern and the University of Michigan."
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Measures Developed To Prevent Health Problems Associated With Biogenic Amines In Wine

Biogenic amines may be one of the factors responsible for symptoms such as headaches, gastro-intestinal disorders, shortness of breath, fall in blood pressure, and even unconsciousness and cardiac arrhythmia in severe cases. Histamine, one of the best known members of this group, can cause serious physical problems. Biogenic amines can be produced in the body by natural metabolic activities but are also ingested in larger quantities with food. They play a special role in microbiologically produced food such as wine, beer, cheese, and sauerkraut. In a joint project Johannes Gutenberg University Mainz (JGU) and the Dienstleistungszentrum Landlicher Raum Rheinpfalz (DLR) have developed measures to identify and reduce biogenic amines in wine, where they can be of particular risk to human well-being.

The goal of these investigations was to avoid high concentrations of biogenic amines in wine. The corresponding investigations were performed in the Institute of Microbiology and Wine Research at Mainz University and the Dienstleistungszentrum Ländlicher Raum Pheinpfalz in Neustadt in a joint project sponsored by the Research Association of the German Food Industry (FEI). "It is important to make efforts in order to reduce biogenic amines in wine, since this problem shall increase in future," predicts Professor Dr. Helmut König of the JGU Institute of Microbiology and Wine Research (IMW). Compared to other microbiologically processed food such as cheese the concentration of biogenic amines in wine may be low. However, their effect on sensitive human beings may be strongly increased during simultaneous ingestion of wine and other problematic food since alcohol significantly impairs the body's ability to metabolize biogenic amines.

Therefore, Helmut König's team and the enologists of the working group of Ulrich Fischer in Neustadt have developed "Practicable Milestones" in order to enable wine-makers to lower the risk of the production of biogenic amines. There currently is no regulatory requirement regarding the upper limits for biogenic amines in wine. However, in view of the health risks and the need to prevent the development of off-flavors that can be caused by some bacteria, wine-makers shall take measures in respect to cellar and wine producing techniques now. The addressed problems may increase in future as a result of climate change, because higher temperatures will promote the growth of undesirable bacteria on the grapes. It has been shown that the production of biogenic amines will be enhanced due to elevated pH values. An earliness of the ripening period of the grapes may lead to an increase of the pH value of the grape juice.

Preventative and curative measures include the use of tested starter cultures, the early detection of the presence of biogenic amine-forming bacteria by molecular methods and procedures to prevent their growth, for example the application of flash pasteurization or the removal of biogenic amines with the help of bentonite or yeast cell walls. The most economic preventive measure is to lower the pH value by adding tartaric acid. This is already permitted in the warmer climate zones of the EU and in non-European countries, but German wine-makers are currently prohibited to apply this measure. However, in the last years an exemption to this regulation was granted.
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High Blood Pressure Ages The Brain

New research led by the University of California (UC) Davis found accelerated brain aging among young middle-aged people with high blood pressure, and even among those whose blood pressure would not be considered high enough to warrant clinical intervention. The researchers say their findings emphasize the need for "early and optimum control of blood pressure".

Reporting in The Lancet's 2 November online issue, senior author Charles DeCarli, professor of neurology and director of the Alzheimer's Disease Center at UC Davis, and colleagues, describe how they found evidence of structural damage in white matter and volume of gray matter in the brains of hypertensive and prehypertensive people in their 30s and 40s that suggests vascular brain injury "develops insidiously over the lifetime with discernible effects".

The study is thought to be the first to show structural damage to the brains of people in young middle age as a result of high blood pressure. Such damage has been linked with cognitive decline in older people.

DeCarli says in a statement:

"The message here is really clear: people can influence their late-life brain health by knowing and treating their blood pressure at a young age, when you wouldn't necessarily be thinking about it."

"The people in our study were cognitively normal, so a lack of symptoms doesn't mean anything."

High Blood Pressure and Cognitive Decline

Normal blood pressure is up to 120/80 ("one twenty over eighty": the first number being the systolic pressure, when the heart is contracting, and the second being the diastolic pressure, when the heart is resting). Prehypertension lies in the range 120-139/80-89, while blood pressures above 140/90 are classed as high (hypertension).

High blood pressure is linked to a 62% higher risk of cerebrovascular disease such as ischemic stroke, and a 49% higher risk of cardiovascular disease. It is the single greatest risk factor for premature death in the US, where it affects some 50 million people.

Previous studies have shown links between high blood pressure and a raised chance of brain injury and wasting away (atrophy), which in turn leads to reduced ability in thinking and memory, and a greater risk of developing dementia. High blood pressure is therefore indirectly an important risk factor for cognitive decline later in life, but it is a modifiable one because it can be treated.

The researchers say there is evidence that treating high blood pressure in middle age can prevent cognitive decline and dementia later.

The Study

For their study, DeCarli and colleagues analyzed data on 579 people taking part in the Framingham Heart Study, a longitudinal investigation that started following the cardiovascular health of people living in Framingham, Massachusetss, over 60 years ago. The study is now in its third generation of participants.

The participants were mostly in their late 30s when they were joined this part of the study, in 2009.

They had their blood pressure taken on entry, and were at that time assigned to one of three groups: normal blood pressure, prehypertensive, or high blood pressure. The researchers also noted their smoking status and if they were taking any medication for blood pressure.

After that, the participants underwent magnetic resonance imaging (MRI) brain scans that took extensive measurements of any white matter injury and gray matter.

Detailed Scans of White Matter

Some of the MRI scans were of a type known as "diffusion tensor imaging" that examines in microscopic detail the architecture of the brain's white matter.

The white matter of the brain comprises the axons, the long filaments that carry electrical signals from one area of the brain to another. Diffusion tensor imaging yields a measure known as "fractional anisotropy", which can sense whether axons are damaged or intact. It can be regarded as a measure of connectivity in the brain.

There is also another type of MRI scan that shows damaged white matter as areas of intense whiteness, or "white-matter hyperintensities".

When combined, the various imaging studies of white and gray matter produced a global measure that allowed comparison of of brain health among the different blood pressure groups.

The Results

When they analyzed the results, the researchers found that the brains of the people in the high blood pressure were significantly less healthy than those of the normal blood pressure group: in fact they looked like they had aged more.

For example, the brain of a typical 33-year-old member of the high blood pressure group, looked similar on the scans to the brain of a typical 40-year-old in the normal blood pressure group.

The more detailed measures showed that the brains of the people in the high blood pressure group had an average 6.5% reduction of fractional anisotropy in the frontal lobes. They also, on average, had 9% less gray matter, in the frontal and temporal lobes, compared to the normal blood pressure group.


The researchers did not propose a mechanism for how high blood pressure might cause the brain to age more quickly. But they did mention that high blood pressure leads to stiffer arteries, which in turn impedes blood flow, so the axons receive less oxygen and essential nutrients.

Lead author Pauline Maillard, a postdoctoral fellow in the UC Davis Department of Neurology, says the findings suggest the microscopic white matter damage that has been linked to high blood pressure in the elderly in other studies may be detectable earlier in life.

This supports the idea that "vascular brain injury may develop insidiously over several decades", says Maillard, and that there is a need for "early and optimum control of blood pressure, which is neither routinely achieved nor subject to testing in randomized controlled clinical trials".

Written by Catharine Paddock PhD
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"Rebooting" MS Drug Succeeds In Trials

Two phase 3 trials of a drug for treating multiple sclerosis (MS) that "reboots" the immune system showed it to be effective in patients who had not responded to first-line therapy: it reduced risk of disability and brain shrinkage. Reporting in the 1 November issue of The Lancet, the researchers describe how alemtuzumab (known commercially as Lemtrada), previously used to treat a type of leukaemia, was able to help people with early MS who relapsed on previous treatments as well as patients who had not yet received any treatment.

Alastair Compston, a professor from the University of Cambridge was principal investigator on both trials and also chaired the Steering Committee that supervised them and an earlier trial. He said in a statement from the University:

"Our research shows the transformative effect that alemtuzumab can have for people with MS."

The findings mark the conclusion of a unique development program for an MS drug that started in Cambridge in 1991. The statement from the University says:

"Never before has an MS drug been tested in clinical outcomes against such a high hurdle, an active first-line drug, in both one phase II trial and two phase III trials; and no drug for MS has been shown to be more effective, in both reducing the risk of disability and reducing the rate of brain atrophy, when compared to another active treatment."

MS is an autoimmune disease where the patient's immune system destroys nerve fibers and their protective insulation, the myelin sheath. The resulting damage stops nerves communicating with each other, leading eventually to loss of the nerve fiber, and progressive physical and cognitive disability.

The disease affects millions of people worldwide, including almost 100,000 in the UK, and 400,000 in the US.

The two randomized, controlled phase 3 trials, reported in two separate papers, are called CARE MS I and CARE MS II. They were both funded by Genzyme (Sanofi) and Bayer Schering Pharma.

The developers expect decisions on drug licences for alemtuzumab by the European and US regulatory authorities to be made in 2013.

In another study reported this week, scientists describe how it may be possible to repair the nerve fiber damage caused by MS.

CARE MS I: Alemtuzumab Versus Interferon beta-1a as First Treatment in RRMS Patients

This three-year trial involved 334 patients with active, early relapsing remitting MS (RRMS) who had not received any treatment for the disease (drug-naïve patients). It tested the performance of alemtuzumab against the first-line drug interferon beta-1a (commercially known as Rebif).

The patients were randomly assigned to one of three groups. One group received interferon beta-1a injections three times a week, and the other two groups each received a different daily intravenous dose of alemtuzumab.

The results showed that alemtuzumab reduced the number of attacks by 55% over and above that achieved by the other first-line drug.

Over a 2-year period, 78% of the patients taking alemtuzumab remained relapse free, compared with 59% in the interferon group.

The percentage of patients whose disability got worse during the trial was slightly lower in the alemtuzumab patients than in the interferon patients, but the result was not statistically significant.

The researchers conclude:

"Alemtuzumab reduced disease activity compared with interferon beta-1a in most of the analysed subgroups. Significantly greater numbers of patients experienced sustained improvement in disability after treatment with alemtuzumab than interferon beta-1a. The efficacy offered by alemtuzumab is a substantial advance in the treatment of multiple sclerosis."

CARE MS II: Alemtuzumab After Failed First-Line Treatment in RRMS Patients

For this 2-year trial, researchers recruited 840 patients agd 18 to 55 with RRMS (from which data from 628 participants was used in the principal analysis), who had received first-line treatment but had recently relapsed during their therapy.

As with the MS I trial, the participants were randomly assigned to received either alemtuzumab or interferon beta-1a. Each patient had their disability assessed every three months by a researcher who did not know which drug they were receiving. They also underwent annual scans to assess lesions and brain shrinkage due to MS.

The results showed that new relapses were reduced by 49% more in the alemtuzumab than the interferon patients.

Over the 2-year period, 65% of patients on alemtuzumab remained relapse free compared with 47% of interferon patients.

Alemtuzumab reduced the risk of acquiring disability by 42% compared to interferon: disability worsened in 20% of interferon patients and 13% of alemtuzumab patients.

Plus, at the end of the study, on average, the patients taking alemtuzumab had less disability than when they started the trial whereas the patients taking interferon had more disability.

The brain scans showed that alemtuzumab not only reduced the number of new lesions, compared to interferon beta-1a, but also reduced the rate of brain shrinkage from the tissue damage caused by MS.

The researchers conclude:

"For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. Suitable risk management strategies allow for early identification of alemtuzumab's main adverse effect of secondary autoimmunity."


Compston says:

"Patients who continue to show disease activity while on their initial therapy are especially difficult to treat. Now, we have shown that alemtuzumab works where first-line drugs have already failed."

The drug "not only reduces the chances of disability associated with MS", but it "may even result in long-term clinical improvements," he adds.

In both trials the main side effect from alemtuzumab was the development of other autoimmune diseases.

Additional work by some of the Cambridge researchers on these trials is looking into how to identify people who are susceptible to this side effect, and they are currently recruiting for a trial that is testing alemtuzumab with a new drug aimed at reducing the adverse reaction.

Written by Catharine Paddock PhD
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Longer Use Of Hormonal Contraception During Midlife Predicts Better Cognitive Function Later

Premenopausal use of hormonal contraceptives may improve the cognitive abilities of women in midlife and for years afterward. This finding may have implications for prevention of declining cognitive function that occurs with advancing age and in diseases such as Alzheimer's. The beneficial effects of hormones increase the longer a woman uses them, as described in a study published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website.*

Kelly Egan, University of Wisconsin School of Medicine and Public Health, and Carey Gleason, PhD, William S. Middleton Memorial Veterans Hospital, Madison, WI, present the results of cognitive performance tests administered to women enrolled in the Wisconsin Registry for Alzheimer's Prevention in the article "Longer Duration of Hormonal Contraceptive Use Predicts Better Cognitive Outcomes Later in Life."

"This study provides preliminary evidence that hormonal contraceptives may have a protective cognitive effect, even years after use is discontinued," says Editor-in-Chief Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health.
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Wednesday, November 7, 2012

Pradaxa (Dabigatran) Bleeding Rates No Higher Than Warfarin, Says FDA

Bleeding rates linked to new use of Pradaxa (Dabigatran) are no higher than they are with new users of warfarin, says a new FDA Drug Safety communication report update (November 2, 2012).

The FDA (Food and Drug Administration) carried out an evaluation on Pradaxa after receiving several post-marketing reports of bleeding among new users.

The Agency says its investigation, which focused on bleeding occurring in the stomach and intestines, as well as bleeding in the brain (intracranial hemorrhage), among new Pradaxa versus warfarin users, found that Pradaxa's bleeding rates are no higher than warfarin's.

The FDA looked at data from insurance claims and the FDA's Mini-Sentinel pilot of the Sentinel Initiative. The results of the Mini-Sentinel assessment show that bleeding rates between the two medications are similar, and consistent with data from the clinical trials that were used during the approval process of Pradaxa (the RE-LY trial).

The Agency says it is continuing to monitor various data sources in the ongoing safety review of Pradaxa.

Medications for patients with non-valvular atrial fibrillation

Patients with non-valvular atrial fibrillation (AF) are at significantly higher risk of developing stroke and blood clots. AF is the most common heart rhythm abnormality, in which the upper chambers of the atria, in the heart, beat irregularly and rapidly.

The two most important medications prescribed to AF patients are warfarin and Pradaxa, to reduce the risk of stroke and blood clots.

While Pradaxa and warfarin are effective, they can cause potentially serious and sometimes fatal bleeding. All anticoagulant medications have this risk.

Recommendations regarding Pradaxa remain unchanged

The FDA emphasizes that Pradaxa "provides an important health benefit when used as directed." It has not altered its recommendations regarding the medication.

Doctors who prescribe Pradaxa must follow the dosing recommendations in the drug label carefully, especially if the patient has renal impairment (improperly functioning kidneys), to minimize the risk of bleeding.

If you have atrial fibrillation and are on Pradaxa, do not stop taking it before discussing with your doctor. If you stop taking the drug suddenly, your risk of stroke will increase. Strokes are potentially serious, permanently disabling and fatal events.

The FDA says it is conducting two planned, protocol-based observational assessments of Pradaxa, which assess patients and evaluate reports of bleeding. Any relevant data that becomes available on bleeding risks related to Pradaxa will be reported immediately, the Agency added.

About Pradaxa (Dabigatran)

Pradaxa (Dabigatran) was approved by the US FDA in October 2010, in capsule form for the prevention of strokes and blood clots in patients with atrial fibrillation. Pradaxa was approved the following year by EMA (European Medicines Agency), in August 2011, for AF patients who are at risk of stroke.

It was the first stroke prevention medication to be approved in 50 years for individuals with AF, according to Pradaxa markers, Boehringer Ingelheim.

Pradaxa (Dabigatran) is a thrombin inhibitor anticoagulant - it inhibits thrombin. Thrombin is a blood enzyme involved in the blood clotting process. Experts believe that it will eventually replace warfarin as the preferred anticoagulant in the majority of cases, because it does not require frequent blood tests for international normalized ratio monitoring, and offers similar efficacy results.

Pradaxa competes with Johnson & Johnson's and Bayer's Xarelto

Bristol-Myers Squibb and Pfizer Inc. have submitted Eliquis (Apixaban) to the FDA for approval. According to many Wall Street analysts, Eliquis is the most impressive of the new generation of oral anticoagulants to replace warfarin.

A Phase III clinical trial (ARISTOTLE) found that patients on Eliquis had better stroke or systemic embolism protection and less bleeding than those on warfarin. Eliquis was shown to reduce stroke or systemic embolism risk by 21%, major bleeding risk by 31%; mortality was reduced by 11%.

Some facts about atrial fibrillation

  • 5 million people are thought to suffer from atrial fibrillation in the USA, and 6 million in the European Union

  • Atrial fibrillation is the most common cardiac arrhythmia (irregular heart condition)

  • Approximately 1 in every 4 people age 40+ years in the USA and Europe are expected to develop AF

  • An AF patient has a five times greater risk of stroke than people without the condition

  • In the USA, 15% of all strokes are thought to be caused by AF

  • Half of all AF patients who have a stroke die within 12 months of the stroke. This figure is considerably higher than stroke cases among non-AF patients. 24% of AF patients die within 30 days of having a stroke
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In Children With 22q11.2 Deletion Syndrome, Higher Anxiety Associated With Poorer Functioning

UC Davis researchers have found that for children with the genetic disorder known as chromosome 22q11.2 deletion syndrome anxiety - but not intelligence - is linked to poorer adaptive behaviors, such as self-care and communication skills, that affect daily life. The developmental syndrome, which is associated with a constellation of physical, cognitive and psychiatric problems, usually is apparent at birth or early childhood, and leads to lifelong challenges.

The study findings suggest that helping children cope with fear-based symptoms may be the best strategy for increasing independence and protecting against psychiatric problems later in life. The article, titled, "An examination of the relationship of anxiety and intelligence to adaptive functioning in children with chromosome 22q11.2 deletion syndrome," is published online in the Journal of Developmental and Behavioral Pediatrics. It will appear in the December 2012 print issue of the journal.

"Our study confirmed our impressions from seeing patients with 22q deletion syndrome that those with more severe anxiety symptoms tend to be most impaired in their everyday functioning," said Kathleen Angkustsiri, lead study author and assistant professor of developmental and behavioral pediatrics with the UC Davis MIND Institute. "It highlights the critical importance of recognizing and treating anxiety in these very vulnerable children."

The disorder also is known as velocardiofacial syndrome, referring to some of the common physical anomalies associated with the disorder, as well as DiGeorge syndrome, after one of the first physicians to describe it. The currently preferred name of chromosome 22q11.2 deletion syndrome identifies the location on the twenty-second chromosome where a small piece of DNA is missing. It is inherited in an autosomal dominant fashion, meaning that the child of a parent with the syndrome has a 50 percent chance of developing the syndrome; however, in 90 to 95 percent of cases, no family history of the syndrome is known, and the mutation arises for the first time in the affected person. The syndrome is estimated to affect about 1 in 2,000-4,000 people, making it the second most common condition after Down syndrome, another genetically based developmental disorder.

Manifestations of the syndrome vary among affected individuals. It may be diagnosed soon after birth because of symptoms related to heart defects as well as anomalies of the mouth, palate and throat, affecting feeding, speech and facial structure. Children with 22q11.2 deletion syndrome have a high prevalence of mental-health disorders such as anxiety and attention deficit hyperactivity disorder (ADHD), and IQs usually are in the borderline-to-low range. In early adulthood, about 30 percent may develop a psychiatric disorder such as schizophrenia.

The study evaluated 78 children with the syndrome, ages seven to 15 years, with a battery of standardized tests related to behavior, anxiety, adaptive functioning and intelligence. Thirty-six typically developing children with no known genetic syndromes were also evaluated for comparison. Assessment involved neuropsychological testing and developmental-behavioral pediatric evaluation of the children as well as parent questionnaires about their child's symptoms.

Mean anxiety scores were found to be significantly higher in children with 22q11.2 deletion syndrome than in typically developing children. Fifty-eight percent of children with the syndrome were found to have at least one elevated anxiety score, although only 19 percent had previously been diagnosed with an anxiety disorder.

In addition, higher anxiety scores correlated with lower adaptive function among children with the syndrome. Adaptive functioning is a measure of age-appropriate everyday living skills surrounding self-care, home and school living, communication and other factors. Specific anxiety subscales that were associated with poorer adaptive behavior included panic-agoraphobia (anxiety associated with unfamiliar environments), physical injury and obsessive-compulsive disorder.

"Anxiety appears to be under-identified by health-care professionals despite known elevated risk in this population," Angkustsiri said. "It is possible that more aggressively recognizing and treating anxiety in these children will prevent more severe problems as they enter adulthood."

For reasons that are not well understood, children with 22q11.2 deletion syndrome have a high risk of developing schizophrenia as they reach adulthood. In the general population, anxiety disorders also are associated with schizophrenia.

No relationship was found in the study between IQ and adaptive skills in children with 22q11.2 deletion syndrome, although an association was found in typically developing children and has been found in other studies of children with developmental disorders. The study authors postulate that the lack of correlation in 22q11.2 deletion syndrome could be explained by anxiety, so that because of fearfulness, children do not attain the maximal adaptive functional skills one might expect given their intellectual potential. In addition, children may not be reaching their optimal learning potential because of being distracted by worries or compulsions during learning opportunities.

The good news is that we have many good interventions to treat anxiety, such as medications and counseling, while cognitive impairments are not as amenable to treatment," said Angkustsiri. "We are hopeful that targeting anxiety can make a difference for children with this disorder, as well as in other vulnerable children."

The researchers are further studying factors that contribute to children with 22q11.2 deletion syndrome either being a "struggler" (characterized by high anxiety and low adaptive functioning) or someone who is coping -- a "coper" -- as well as interventions that may help the strugglers to become copers.

"This study provides an important key to significantly helping children with 22q deletion syndrome cope better with everyday life and improve their outcomes," said Tony J. Simon, principal investigator of the study and professor of psychiatry and behavioral sciences at UC Davis and the MIND Institute.

"The effects of anxiety should not be underestimated, and physicians caring for children with special needs should be proactive in diagnosing and treating it."

The team recently has started the "22q Healthy Minds Clinic" in order to put this research into practice. A team including a developmental-behavioral pediatrician or child psychiatrist, child psychologist, and cognitive neuroscientist evalutes children with 22q11.2 deletion syndrome and provides recommentations for intervention.
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Indoor Laundry Drying Could Be Bad For Your Health

A combination of prolonged wet weather and reducing use of tumble dryers as a way to cut fuel bills, may encourage people to dry more clothes indoors, for instance on drying frames or by draping on radiators. But according to researchers in Scotland, this could pose health risks by increasing moisture that encourages moulds and dust mites, which is bad for people prone to asthma.

Also, while the intention may be to save energy and cost, that is not necessarily the result, say the researchers, from the Mackintosh Environmental Architecture Research Unit (MEARU) at The Glasgow School of Art, working with Strathclyde and Caledonian universities, because in order to dry off the 2 litres that the average load of washing releases into the air, people often turn up the heating.

The three-year research project, titled "Environmental Assessment of Domestic laundering", was funded by the Engineering and Physical Sciences Research Council (EPSRC). A report and press statement were released on 2 November.

Report co-author, Colin Porteous, a professor at MEARU, says:

"Because of increased awareness of the energy consumption of tumble dryers many people are choosing to dry clothes passively within their home."

"This results not only in a severe energy penalty, because of increased heating demand, but also a potential health risk due to higher moisture levels," he adds.

Socks drying indoors
Researchers suggest a strong correlation between drying laundry indoors and increased spore growth, which can exacerbate symptoms for sufferers of asthma, hay fever and other allergies.

The researchers examined the laundry habits of residents in a wide demographic mix living in social housing in the West of Scotland, and also carried out a detailed analysis of air quality and energy consumption.

They concluded indoor drying of laundry poses environmental, economic and health problems, and the tendency in the UK toward building smaller, more airtight homes, only serves to make things worse.

In ill-ventilated rooms, putting clothes on radiators to dry can account for up to a third of the moisture in the air, and creates ideal conditions for mould spores to grow and dust mites to thrive. Both these conditions are known triggers of asthma.

The researchers also point out that indoor drying of clothes that contain fabric conditioner is likely to increase the amount of cancer-causing chemicals in the air.

Indoor laundry drying also leads to increased use of energy, as radiators are often turned up to help the drying process, and/or windows are opened. This just worsens fuel poverty, already a major issue in the West of Scotland, say the researchers.

The team recommends people dry their laundry outdoors whenever possible, or use energy-efficient, condensing tumble dryers. If you have to dry your clothes indoors, then place them by a south facing window (the message is for people in the UK), using natural light and heat. An even better method is to place the clothes on a south-facing balcony, if you have one.

They also suggest, when creating new housing stock, planners and builders should make sure the designs cater for ways of drying laundry that do not contribute to poor air quality. The researchers have published a design guide with suggestions like: upgrading balconies and sunspaces, ensuring new homes have a drying space with its own heating and ventilation, communal laundry and drying facilities, and installing energy-efficient appliances.

The team is now discussing its findings with social housing authorities, with a view to their proposals being adopted as Housing Associations upgrade existing stock and build new homes.

However they argue more sweeping changes are necessary, including updating the Building Regulations so they apply to all new housing. Such a move would have many benefits, says Porteous:

"Our research gives strong justification for the changes both in terms of health and wellbeing, and associated economic impacts. It is our hope that current statutory and advisory standards will be modified to take them on board ensuring a healthy and economically sustainable living environment."
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Repair Of Multiple Sclerosis Brain Damage May Be Possible

In what they describe to the press as a "life-changer" for millions of people with the disease, researchers in the US report this week a study where they discovered blocking an enzyme in the brain may help repair the damage associated with multiple sclerosis (MS), and other brain diseases.

The findings are due to be published online this week in the Annals of Neurology.

Myelin Damage

In MS, the protective sheath or myelin around nerve fibers is damaged or destroyed, disrupting the ability of nerve cells to communicate with each other. This process, called demyelination, is what causes the range of sensory, movement and cognitive problems typical of the disease.

Lead researcher of the new study, Larry Sherman, a professor at Oregon Health & Science University, heads a lab that had been studying MS and other disorders where myelin gets damaged for nearly 15 years.

Back in 2005, Sherman's team published a study in Nature Medicine reporting their discovery that a sugar molecule called hyaluronic acid appears to play a key role in demyelination. They found large deposits of hyaluronic acid at sites of myelin damage in humans and animals, and suggested the sugar itself stops remyelination, or repair of damaged myelin, by preventing the cells that form the myelin from differentiating at the damage sites.

Today's news comes as The Lancet this week reports two successful trials of a new drug for MS that "reboots" the immune system so it does not attack the nerve fibers.

Enzyme Prevents Myelin Repair

MRI of brain showing multiple sclerosis
Multiple sclerosis is a chronic disease that attacks the brain, spinal cord and optic nerves
Now, in their latest findings, Sherman and colleagues propose that it is not hyaluronic acid, but the compounds it breaks down into when in the presence of an enzyme called hyaluronidase, that prevents remyelination or myelin repair.

They found very high levels of the enzyme in brain lesions of patients with multiple sclerosis and in the nervous systems of mice with an MS-like disease.

When they blocked the activity of the enzyme in the mice with the MS-like disease, myelin-forming cell differentiation was restored.

But perhaps the more significant result of the study was that the drug the researchers used to restore myelin repair, also led to improved nerve cell function.

New Target for Drugs to Promote Myelin Repair

"What this means is that we have identified a whole new target for drugs that might promote repair of the damaged brain in any disorder in which demyelination occurs," says Sherman in a statement.

"Any kind of therapy that can promote remyelination could be an absolute life-changer for the millions of people suffering from MS and other related disorders," he adds.

Sherman, who is also a senior scientist in the Division of Neuroscience at the Oregon National Primate Research Center, says the next step is to develop a drug that specifically targets the effect of hyaluronidase.

He says the drug they used in the study would not be suitable for humans because it has potentially serious side effects. But a drug designed just for blocking hyaluronidase would most likely have few, if any, side effects he suggests.

The findings are likely to impact research and drug development for MS and a range of other disorders involving demyelination, including complications arising from premature birth.

Not an MS Cure

Sherman also makes the point that blocking the enzyme does not constitute a cure for MS. Other factors could be contributing to demyelination in MS and related diseases. But the discovery of the enzyme, and finding a way to block it, may at the very least "lead to new ways to promote the repair of brain and spinal cord damage either by targeting this enzyme alone or by inhibiting the enzyme in conjunction with other therapies," he says.

Grants from the National Institutes of Health, Fast Forward, LLC (a subsidiary of the National Multiple Sclerosis Society), the Laura Fund for Multiple Sclerosis Research, the March of Dimes Birth Defects Foundation and the American Heart Association, helped fund the study.
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