RxPG News : Neurosciences

Multicenter EPIC study found that the FiberNet Embolic Protection System had a 97.5% success rate

Mon, 01 Mar 2010 12:57:02 PST

( from http://www.rxpgnews.com ) A multicenter EPIC (FiberNet® Embolic Protection System in Carotid Artery Stenting Trial) study found that the FiberNet Embolic Protection System (EPS) had a 97.5% success rate when used in patients undergoing carotid artery stenting (CAS). Full findings are published early online in Catheterization and Cardiovascular Interventions, the official journal of The Society for Cardiovascular Angiography and Interventions.

Carotid artery stenosis or carotid artery disease occurs when plaque forms in the carotid artery, causing it to narrow and increasing risk for ischemic stroke. According to the National Institutes of Health, a blockage of a blood vessel is the most frequent cause of stroke, responsible for 80% of the estimated 700,000 strokes in the U.S. annually. Carotid artery stenosis is often treated with CAS, the placement of a tiny flexible tube in the diseased vessel.

Unfortunately, stenting procedures carry the risk of embolism, where plaque breaks away from the site of formation and blocks another artery downstream. Embolic protection devices have emerged to prevent strokes by catching the debris that may break away during CAS surgery. Over the past decade, several protection systems have emerged with varying degrees of success.

A research team led by Subbarao Myla, M.D, FSCAI, evaluated the safety and efficacy of this new design concept for embolic protection during CAS. The study was designed to demonstrate that the 30-day major adverse event (MAE) rate of all death, stroke, and myocardial infarction (MI) is significantly less than the performance goal of 8.3% from the ARCHeR 3 results.

The trial enrolled 237 patients with a mean age of 74 years from 26 centers across the U.S. and Europe. Study participants were 64% male and 20% had symptomatic carotid artery disease (CAD). Results indicate the combined MAE rate at 30 days following carotid endarterectomy (CEA) for all death, stroke and heart attack was 3.0%.

"The 30-day death, stroke, and MI rate of 3.0% is encouraging," says Dr. Myla. The researchers concluded that the FiberNet EPS, when used with commercially available stents, produced low stroke rates following CAS in high surgical risk patients with CAD.

Dr. Myla describes the team's experience with the new embolic protection device: "The low crossing profile and integration of a primary guidewire shortened procedure time, and facilitated lesion crossing and filter placement, especially in the presence of tortuous anatomy. The 0.014" guidewire tip demonstrated good torque response and the guidewire provided excellent support…it was ideal for procedures in which tortuosity would preclude placement of a more structured DPD with a stiff delivery catheter. Conformability of the expanded fiber network to the vessel wall and the short landing zone of the device made it ideal for challenging anatomy distal to the lesion. Anecdotally, investigators have commented the FiberNet EPS resulted in fewer vessel spasms."

Blacks more likely to have undiagnosed key stroke risk factor, have higher stroke incidence

Fri, 26 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Blacks are more likely to have an undiagnosed key risk factor for stroke and are more likely to have a stroke than whites, according to two studies presented at the American Stroke Association's International Stroke Conference 2010.

In two separate reports using data from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, researchers found significant racial and geographic disparities in stroke incidence and in receiving the recommended treatment to prevent stroke.

The REGARDS study enrolled 30,239 participants across the United States, age 45 or older, between January 2003 and October 2007 and continues to follow them for health events.

In the first analysis (Meschia, Abstract P160), researchers found that among 432 study participants (88 blacks; 344 whites) who had atrial fibrillation (AF), blacks were two-thirds less likely to know they had the disorder and three-fourths less likely to be treated with the gold standard of care, the blood thinner warfarin.

These disparities are a problem, said James F. Meschia, M.D., the study's lead author and a neurologist at the Mayo Clinic in Jacksonville, Fla. For patients who are able to take warfarin, it makes a huge difference. Stroke trials have shown that warfarin reduces the risk of stroke by 60 percent.

Meschia notes that warfarin is not for everyone, because of the risk of bleeding. AF, which affects more than 2.2 million Americans, occurs when one of the heart's upper chambers quivers and doesn't effectively pump blood out, which allows blood to pool and clot. These dangerous clots can cause stroke if they lodge in an artery in or leading to the brain. This research is also simultaneously published in Stroke: Journal of the American Heart Association.

Because atrial fibrillation is such a powerful risk factor for stroke, these findings suggest that lower awareness of atrial fibrillation and reduced likelihood of treatment among blacks may place blacks at higher risk of a stroke, which in turn could contribute to the higher stroke mortality among blacks, Meschia said.

The healthcare system needs to better screen for and inform people about whether they have AF, and more study is needed to shed light on the causes of the disparity in warfarin treatment, he said.

In the second analysis (Howard, abstract P158), researchers provide the first national data describing racial and regional disparities in stroke incidence. Researchers reviewed data on about 26,580 REGARDS participants who had not had a stroke at baseline and documented 299 strokes during the almost five-year period.

Total fat, trans fat linked to higher incidence of ischemic stroke

Wed, 24 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Post-menopausal women who reported consuming the most daily dietary fat had a 40 percent higher incidence of clot-caused strokes compared to women who ate the least amount, according to research presented at the American Stroke Association's International Stroke Conference 2010.

The incidence of ischemic stroke also increased by 30 percent in the quartile of women consuming the highest daily amount of trans fat (average intake 7 grams per day) compared to those who consumed the least (average 1 gram/day). Two common sources of trans fat are processed foods and fried foods.

Ischemic strokes are caused by blockages in blood vessels in or leading to the brain.

We found positive associations between total fat intake and ischemic stroke incidence and between trans fat intake and ischemic stroke incidence, said Sirin Yaemsiri, M.S.P.H., a doctoral student in the department of epidemiology in the Gillings School of Global Public Health at the University of North Carolina in Chapel Hill.

The study is the first to examine the associations of different fats and different subtypes of ischemic stroke in post-menopausal women, who face a higher stroke risk than men of a similar age.

Evidence from other studies shows that different types of fat have different effects on the incidence of coronary heart disease (CHD), with trans fat implicated in the development of CHD. However, studies of ischemic stroke and fat have been inconclusive, possibly because earlier studies had small numbers of ischemic stroke cases.

Before menopause, women have a lower risk of stroke compared to men of similar age, a situation that reverses after menopause, Yaemsiri said.

The analysis included data on 87,230 post-menopausal women ages 50 to 79 who participated in the Women's Health Initiative (WHI) Observational Study, a project sponsored by the National Institutes of Health and the National Heart, Lung and Blood Institute. The women answered a food frequency questionnaire when they entered the study and were followed for an average of 7.6 years, the researchers said. During that time, 1,049 ischemic strokes occurred.

Researchers looked for links between dietary fat intake and four ischemic stroke subtypes, which were characterized by their size or point of origin. However, the data on ischemic stroke subtypes fell short of statistical significance, perhaps because strokes are difficult to characterize and 43 percent (445 cases) of the ischemic strokes in the study were of unknown type, Yaemsiri said.

Researchers divided the women into quartiles based on the amount of total dietary fat and types of fat (saturated fat, monounsaturated fat, polyunsaturated fat and trans fat) they reported consuming per day.

Variables included age, race, smoking status, physical activity, alcohol or aspirin use, body mass index, hormone therapy, heart disease history, diabetes, systolic blood pressure and whether the women took medication for high blood pressure or to reduce cholesterol, vitamin E supplementation, fruit/vegetable intake, total calories and dietary fiber.

Women in the top quartile for total fat intake had an average intake of 86 grams of total fat per day. Those in the lowest quartile consumed an average of 26 grams a day.

I think our findings support the American Heart Association recommendations for keeping trans fat intake at less than 1 percent of energy, said Ka He, M.D., Sc.D., M.P.H., senior author of the study and associate professor of nutrition and epidemiology at the UNC Gillings School of Global Public Health.

Vitamin B3 shows early promise in treatment of stroke

Wed, 24 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) An early study suggests that vitamin B3 or niacin, a common water-soluble vitamin, may help improve neurological function after stroke, according to Henry Ford Hospital researchers.

When rats with ischemic stroke were given niacin, their brains showed growth of new blood vessels, and sprouting of nerve cells which greatly improved neurological outcome.

Now research is underway at Henry Ford to investigate the effects of an extended-release form of niacin on stroke patients. Henry Ford is the only site nationally conducting such a study.

If this proves to also work well in our human trials, we'll then have the benefit of a low-cost, easily-tolerable treatment for one of the most neurologically devastating conditions, Michael Chopp, Ph.D., scientific director of the Henry Ford Neuroscience Institute.

Dr. Chopp will present results from the animal model study at the International Stroke Conference in San Antonio.

According to the National Stroke Association, stroke is the third-leading cause of death in America and a leading cause of disability.

Ischemic strokes occur as a result of an obstruction within a blood vessel supplying blood to the brain. Ischemic stroke accounts for about 87 percent of all cases. One underlying condition for this type of obstruction is the development of fatty cholesterol deposits lining the vessel walls.

Niacin is known to be the most effective medicine in current clinical use for increasing high-density lipoprotein cholesterol (HDL-C), which helps those fatty deposits.

Dr. Chopp and his colleagues found that in animals niacin helps restore neurological function in the brain following stroke.

In 2009, stroke physicians at Henry Ford Hospital published research which showed that HDL-C is abnormally low at the time stroke patients arrive at the hospital.

Dr. Chopp's research found that in animals, niacin increased good cholesterol (HDL-C), which increased blood vessels in the brain and axonal and dendritic growth leading to a substantial improvement in neurological function.

Niacin essentially re-wires the brain which has very exciting potential for use in humans, says Dr. Chopp. The results of this study may also open doors in other areas of neurological medicine, including brain injury.

Andrew Russman, D.O., is the principal investigator of the team at Henry Ford Hospital who will evaluate in clinical trials whether niacin improves recovery for human stroke patients.

If we are able to prove that treating patients with niacin helps to restore neurological function after stroke, we're opening a whole new avenue of treatment for the leading cause of serious long-term disability in adults, says Dr. Russman.

Changes during menopause increases risk of heart disease and stroke

Tue, 23 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO- When women hear the word menopause, they often think about hot flashes, hormone shifts and mood swings. But what about heart disease? Studies show a woman's risk of heart disease intensifies drastically around the time of natural menopause, which for most women is around the age of 50. This news may come as a surprise, but experts explain that understanding risk factors is an important first step, and reassure women that there are ways to lower your risk.

Many women younger than 50 have not yet gone through menopause and still have high levels of the female hormone estrogen in their blood, which is thought to help protect the heart. After menopause, however, the levels of estrogen in a woman's body drop significantly and can contribute to the higher risks of cardiovascular disease, explains Vera Rigolin,MD, associate director of the Center for Women's Cardiovascular Health in the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital.

Weight gain is also a factor that may play a role in postmenopausal risk of heart disease. Maintaining a healthy weight often becomes difficult after your body experiences a change in hormone levels. Extra mass can take a toll on the body causing physical inactivity, high blood pressure, diabetes, and high cholesterol, all risk factors that can lead to heart attack and stroke.

Detecting heart disease in women can be difficult. Many women are unaware that symptoms of the disease may differ from those of men. Although women often experience chest discomfort when presenting with a heart attack, they commonly have other, more subtle symptoms, including fatigue, nausea, shortness of breath, jaw pain and general discomfort in the chest and abdominal area.

In some women, plaque can build in the smallest blood vessels called the microvascular circulation. These blockages do not show up in an angiogram, says Rigolin. In these cases, we often use Magnetic Resonance Imaging (MRI) with medication to visualize blood flow within the small blood vessels when other standard tests do not provide us answers.

Women, especially those who are menopausal can reduce the risk of heart disease by adopting a healthy lifestyle.

If you are a smoker, quit immediately and avoid second hand smoke. Eat a diet rich in fruits and vegetables and exercise at least three times per week to maintain a healthy body weight, says Rigolin.

Rigolin also recommends visiting your health care provider at least once per year to have your blood pressure, blood sugar and cholesterol levels checked.

High prevalence of AF found among cross-country skiers

Tue, 09 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Next month, in the Norwegian town of Rena, 12,000 elite cross-country skiers will line up for this year's Birkebeiner ski marathon, an annual endurance race which will take them through 54 kilometres of snow-covered countryside to the winter sports resort of Lillehammer. The race has been run almost every year since 1932, and in 1976 almost 150 participants were invited to take part in a long-term study designed to discover the extent of latent heart disease in these elite cross-country skiers. Now, after some 30 years, the results of the follow-up study have been published and suggest that long-distance competition skiers - as well as other endurance athletes - are at an unusually high risk of atrial fibrillation, the most common abnormality of the heart's beating rhythm.(1)

Results showed that participants in the study are at a high risk of atrial fibrillation (AF) without known structural heart disease or other known causes (a condition termed lone AF). A prevalence of 12.8% found among the skiers who completed the study's investigations in 1976, 1981 and 2004-2006, when echocardiographic (ECG) and heart rate tests were performed at rest and at exercise. In the general population studies have found the prevalence of AF to be as low as 0.5%, with rates only rising to around 15% in men over the age of 75.

When the study began in 1976 participants were classified according to age - group I 26-33 years, group II 43-50 years, and group III 58-64 years; all had been competing in long-distance skiing events and were in the top 25% for age related performance. When the final follow-up examinations were performed during 2004-2006, a large proportion from group III (28/39) had died, leaving 78 of the original 122 available for further tests and questioning.

This analysis showed that 13 of those 78 skiers (16.7%) had experienced AF at some time during the 28-30 years of follow-up, with a current prevalence of 12.8% AF with no other known heart disease. The latter, say the investigators, is the highest prevalence yet described in long-term endurance sport practitioners. In age group I the prevalence was found to be 18.2%. The mean age at which the AF occurred was 58 years.

The study also detected two characteristics in the skiers which may predict their risk of AF: a slow heart rate at rest (known as bradycardia) and a large left atrium of the heart.(2) Both have been suggested in previous studies as common findings in the hearts of endurance athletes. However, the study found no association between the years of training in cross-country skiing (an average of 36 years in this study) and the occurrence of AF. As a result, the authors advise that there is still not enough evidence to recommend a specific age to reduce training volume and/or intensity. However, they do recommend that after the appearance of AF practice should be stopped or reduced until rhythm control is attained.

Disturbances in heart rhythm, which are the most common cause of sudden cardiac death, represent one of the major cardiovascular reasons for hospital admission. Professor Josep Brugada, President of the European Heart Rhythm Association of the ESC (and Medical Director at the Hospital Clinic in Barcelona), has described their impact as enormous, noting that around 5% of all medical expenditure in Europe is related to atrial fibrillation, the most common arrhythmic condition.

So far, only three case-control studies have found a higher prevalence of AF in athletes than in controls. However, a population-based study from 2009 showed that those with the highest level of endurance training also had the highest prevalence of AF.

Studies aiming to find an explanation for a higher AF prevalence have also found that the size of the heart muscle and chambers was larger in athletes than in controls, and this seemed a predictor for AF.

Commenting on the findings from the Birkebeiner study, principal investigator Dr Jostein Grimsmo from the Feiring Heart Clinic in Norway, agreed that enlargement of the heart's left atrium - along with bradycardia - appeared to be an important risk factor for AF among long-term endurance cross-country skiers. This atrial enlargement, he said, is the heart's adaptation to endurance training.

As many as 20% of young competitive athletes have been found to have an enlarged left atrium in some studies, said Dr Grimsmo. But we are not aware of any documentation of such a high prevalence as we have found either in athletes or in controls under the age of 75!

But despite our findings, he added, we still can't say why some athletes end up with AF and others don't. Genetic factors predisposing to 'athlete's heart', with enlarged cardiac dimensions and a slow heart rate, may be important as risk factors. And while it may be that prolonged endurance training over many years may not always be good for the heart, we do not yet have sufficient evidence to make specific recommendations.

NHLBI funds preclinical tests on devices for infants and children with congenital heart defects

Thu, 04 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, has awarded four contracts totaling $23.6 million to begin preclinical testing of devices to help children born with congenital heart defects or those who develop heart failure. The four-year program is called Pumps for Kids, Infants, and Neonates (PumpKIN).

Each year in the United States, nearly 1,800 infants die as a result of congenital heart defects and another 350 develop heart disease, which leads to heart failure for many. Approximately 60 infants and children under 5 years old who are placed on the heart transplant waiting list die each year before receiving one. Mechanically assisted circulatory support could be used to sustain these young patients as they seek to recover or wait to receive a heart transplant.

This research seeks to develop technologies to expand life-saving options for infants and children born with congenital heart defects or those who develop heart failure, said NHLBI Acting Director Susan B. Shurin, M.D., a pediatrician. The NHLBI is committed to saving the lives of our youngest patients. Well-designed circulatory support devices are expected to substantially improve the outcomes of the infants and young children who need them as they seek to recover or wait to receive a heart transplant.

The options for chronic circulatory support devices for infants and young children are limited, and all have substantial risks for serious adverse events such as infection, stroke, and device failure. With this in mind, the NHLBI launched the Pediatric Circulatory Support Program in 2004 by funding the development of five novel circulatory support devices for infants and young children with congenital and acquired cardiovascular disease.

The PumpKIN program is the next phase of NHLBI support for the development and clinical realization of these devices. The program's goal is to complete the needed animal studies and other tests in artificial environments for the most promising devices in order to gain approval from the FDA to begin clinical testing.

Devices in the program will provide suitable circulatory support for newborns, older infants, and children less than 55 pounds who experience heart failure due to congenital and acquired cardiovascular disease. They are designed to supply adequate blood flow to prevent organ damage while minimizing the risk of blood vessel damage, infection, breakdown of red blood cells, excessive bleeding, brain damage, and dangerous blood clots. The devices are intended to support circulation in pediatric patients for one to six months, be sufficiently small and reasonably portable, and be able to be routinely positioned and functioning in less than one hour, among other specifications.

Similar devices are used in adults, Shurin noted. As an adult, your heart is normally about the size of your fist; devices for small children require radically different designs from adult devices to adapt to the differences in the size of the patients.

The program will test ventricular assist devices (VADs) and advanced extracorporeal membrane oxygenator (ECMO) devices. The VADs in the PumpKIN program are very small rotary pumps which are implanted to provide circulatory support for extended periods of use. They work by drawing blood from the heart and pumping it to the body. ECMO devices circulate and supply oxygen to the blood, and are commonly used for patients who need both heart and lung support. For ECMO devices, tubes connecting the patient to the device are placed directly into large blood vessels near the base of the neck. Blood is drawn from the right side of the heart, pumped through the oxygenator, and then returned to the body on the left side of the heart so the oxygen-rich blood can be delivered throughout the body.

The contractors will conduct all preclinical animal testing and analysis in the first three years of the contract. During the third year, they will partner with a data coordinating center (the contract for which is still to be awarded) to complete the necessary activities to seek FDA approval to begin the clinical trial.

Study prompts calls for Europe-wide salt legislation

Tue, 26 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) This study provides excellent ammunition both to convince patients about the benefits of reducing their individual salt intakes and also to persuade the EU of the urgent need to introduce legislation to restrict the salt content of processed foods, said ESC spokesman Professor Frank Ruschitzka, a cardiologist and hypertension specialist from the University of Zurich, Switzerland.

This study represents the evidence that a reduction of salt intake not only lowers blood pressure but also prevents cardiovascular events. The case for population-wide salt reduction is now compelling, he added.

In the paper, Kirsten Bibbins-Domingo and colleagues, from the University of California, San Francisco, USA, undertook a computer simulation showing the effects of population wide reductions of dietary salt intakes in all adults aged 35 to 85 years in the USA. Reducing dietary salt intake by 3 g per day (1200mg less sodium per day) could result in 60,000 to 120,000 fewer cases of heart disease , 32,000 to 66,000 fewer strokes and 54,000 to 100,000 fewer heart attacks.

A reduction in dietary salt of 3g per day, the authors went on to say, would have approximately the same effect on reducing cardiac events as a 50 % reduction in tobacco use, a 5% reduction in body mass index among obese adults or the use of statins to treat people at low or intermediate risk for CHD events. Furthermore, reducing dietary salt intakes by 3g per day would save $10 billion to $ 24 billion in annual health care costs.

ESC spokesperson Professor Giuseppe Mancia, from the University of Milano-Bicocca, St. Gerardo Hospital (Milan, Italy), said the annual health cost savings outlined in the study would be likely to prove a persuasive argument for both the EU and individual European governments.

Recent studies clearly show that salt reduction reduces cardiovascular deaths.4

Epidemiological studies have also firmly established that increased intakes of salt directly increase blood pressure. High salt intakes are believed to exert their detrimental effects by influencing fluid retention, which in turn increases blood pressure. But it's important for patients to appreciate that not all cardiovascular problems relating to salt are mediated through hypertension. Salt can have an adverse effect on cardiovascular health, even among people with normal blood pressure, said Ruschitzka.

Salt intakes across Europe are known to vary widely, ranging from 8.6 g of salt per day in the UK, to around 12 g salt in Croatia. Even the best intakes, however, are falling widely short of the ESC Clinical Practice Guidelines for the Management of Arterial Hypertension(2), based on WHO data, that recommend that only 5g of salt should be consumed per day. This amounts to just one teaspoonful.

While individuals may use salt sparingly at home, around 75 % of the salt we eat is already in the food we buy. This, says the ESC, underlines the need for legislation to lay down guidelines. The reality of international food production in Europe means that such public health initiatives need to be tackled on a European wide basis, rather than an individual country basis, said Ruschitzka.

Furthermore, added Mancia, concerted action is usually more effective. It has the advantage of preventing country to country inequalities and furthermore prevents the reinvention of the wheel in each individual country, he said.

But calls for legislation do not mean that physicians should stop their efforts to persuade patients to introduce individual changes in lifestyle. Patients, they stress, need to be taught about the importance of reducing salt in their cooking and also for the need to check food labels. People need to learn to appreciate that the salt contents can vary widely even in the same product. Take bread, for example. Recent research from Consensus Action on Salt and Health (a charity lobbying food manufacturers in the UK) has shown that the highest salt content was 3g salt per 100 g of bread, while the lowest was 0.7 g salt per 100g.

To improve cardiovascular health, salt reduction cannot be undertaken in isolation. It needs to be remembered that lifestyle measures such as smoking cessation, weight reduction, increased physical exercise, and eating plenty of fruit and vegetables are also important for reducing cardiovascular disease, said Mancia.

Salt will again be on the agenda with World Salt Awareness Week 2010 , which runs from February 1- 7 (3). The week is being run by World Action on Salt and Health (WASH), a global group that works with governments to highlight the need for widespread introduction of population based salt reduction strategies.

Much can be done to reduce salt intakes through public health policy, say WASH. They cite the success of Consensus Action on Salt and Health (CASH), launched in 1996 to encourage food manufacturing companies in the UK to make voluntary reductions in their salt content. Since the start of the policy salt intakes among UK adults (calculated from 24-hour urine samples) have fallen from 9.5 to 8.6 g per day.

In July 2009, WASH surveyed over 260 food products available around the world from food manufacturers such as KFC, McDonalds, Kellogg's, Nestle, Burger King and Subway, finding surprisingly wide spread variations. For example, Kellogg's All Bran for sale in France, Norway, Sweden and the Netherlands contains 1.30 g salt per 100 g compared to salt levels of 0.65 g per 100g for the product in the US. Such data underlines the urgent need to eradicate country to country inequalities, and bring everyone up to the highest possible standards.

The paper by Bibbins-Domingo and colleagues is an urgent call to action. Policy makers in the European Community need to implement public health interventions that result in reductions in salt intake now. Reducing the salt content of our unneccesarily oversalted ,processed food is an inexpensive, yet highly effective public health intervention that we can't afford to miss, concluded Ruschitzka.

Mental lapses signal Alzheimer's disease

Mon, 18 Jan 2010 13:42:35 PST

( from http://www.rxpgnews.com ) Older people who have "mental lapses," or times when their thinking seems disorganized or illogical or when they stare into space, may be more likely to have Alzheimer's disease than people who do not have these lapses, according to a study published in the January 19, 2010, print issue of Neurology, the medical journal of the American Academy of Neurology.

These mental lapses, also called cognitive fluctuations, are common in a type of dementia called dementia with Lewy bodies, but researchers previously did not know how frequently they occurred in people with Alzheimer's disease and, equally important, what effect fluctuations might have on their thinking abilities or assessment scores.

The study involved 511 people with an average age of 78. Researchers interviewed the participant and a family member, evaluated the participants for dementia and tested their memory and thinking skills.

People with three or four of the following symptoms met the criteria for having mental lapses:

Feeling drowsy or lethargic all the time or several times per day despite getting enough sleep the night before
Sleeping two or more hours before 7 p.m.
Having times when the person's flow of ideas seems disorganized, unclear, or not logical
Staring into space for long periods

A total of 12 percent of the people with dementia in the study had mental lapses. Of 216 people with very mild or mild dementia, 25 had mental lapses. Of the 295 people with no dementia, only two had mental lapses.

Those with mental lapses were 4.6 times more likely to have dementia than those without mental lapses. People with mental lapses also tended to have more severe Alzheimer's symptoms and perform worse on tests of memory and thinking skills than people who did not have lapses.

"When older people are evaluated for problems with their thinking and memory, doctors should consider also assessing them for these mental lapses," said senior study author James E. Galvin, MD, MPH, of Washington University School of Medicine in St. Louis, who is a member of the American Academy of Neurology.

Artificial muscle to help in blinking in patients with eyelid paralysis

Mon, 18 Jan 2010 12:44:35 PST

( from http://www.rxpgnews.com ) Surgeons from UC Davis Medical Center have demonstrated that artificial muscles can restore the ability of patients with facial paralysis to blink, a development that could benefit the thousands of people each year who no longer are able to close their eyelids due to combat-related injuries, stroke, nerve injury or facial surgery.

In addition, the technique, which uses a combination of electrode leads and silicon polymers, could be used to develop synthetic muscles to control other parts of the body. The new procedure is described in an article in the January-February issue of the Archives of Facial Plastic Surgery.

“This is the first-wave use of artificial muscle in any biological system,” said Travis Tollefson, a facial plastic surgeon in the UC Davis Department of Otolaryngology – Head and Neck Surgery. “But there are many ideas and concepts where this technology may play a role.”

In their study, Tollefson and his colleagues were seeking to develop the protocol and device design for human implantation of electroactive polymer artificial muscle (EPAM) to reproducibly create a long-lasting eyelid blink that will protect the eye and improve facial appearance. EPAM is an emerging technology that has the potential for use in rehabilitating facial movement in patients with paralysis. Electroactive polymers act like human muscles by expanding and contracting, based on variable voltage input levels.

For people with other types of paralysis, the use of artificial muscles could someday mean regaining the ability to smile or control the bladder. Reanimating faces is a natural first step in developing synthetic muscles to control other parts of the body, said UC Davis otolaryngologist Craig Senders.

“Facial muscles require relatively low forces, much less than required to move the fingers or flex an arm,” said Senders.

Blinking is an essential part of maintaining a healthy eye. The lid wipes the surface of the eye clean and spreads tears across the cornea. Without this lubrication, the eye is soon at risk of developing corneal ulcers that eventually can cause blindness.

Involuntary eye blinking is controlled by a cranial nerve. In most patients with permanent eyelid paralysis, this nerve has been injured due to an accident, stroke, or surgery to remove a facial tumor. Many have no other functioning nerves nearby that can be rerouted to close the eyelid. Others were born with Mobius syndrome, characterized by underdeveloped facial nerves. These patients are expressionless and can neither blink nor smile.

Eyelid paralysis currently is treated by one of two approaches. One is to transfer a muscle from the leg into face. However, this option requires six to10 hours of surgery, creates a second wound, and is not always suitable for elderly or medically fragile patients.

The other treatment involves suturing a small gold weight inside the eyelid. The weight closes the eye with the help of gravity. Though successful in more than 90 percent of patients, the resulting eye blink is slower than normal and cannot be synchronized with the opposite eye. Some patients also have difficulty keeping the weighted lid closed when lying down to sleep. In the United States, an estimated 3,000 to 5,000 patients undergo this surgery every year and therefore might benefit from an alternative treatment.

For their study, Senders and Tollefson used a novel alternative method for eyelid rehabilitation in permanent facial paralysis. They used an eyelid sling mechanism to create an eyelid blink when actuated by an artificial muscle. Using cadavers, the surgeons inserted a sling made of muscle fascia or implantable fabric around the eye. Small titanium screws secured the eyelid sling to the small bones of the eye. The sling was attached to a battery-operated artificial muscle. The artificial muscle device and battery were into a natural hollow or fossa at the temple to disguise its presence.

Senders and Tollefson found that the force and stroke required to close the eyelid with the sling were well within the attainable range of the artificial muscle. This capability may allow the creation of a realistic and functional eyelid blink that is symmetric and synchronous with the normal, functioning blink. A similar system also could give children born with facial paralysis a smile.

The three-layered artificial muscle was developed by engineers at SRI International of Palo Alto, Calif., in the 1990s. Inside is a piece of soft acrylic or silicon layered with carbon grease. When a current is applied, electrostatic attractions causes the outer layers to pull together and squash the soft center. This motion expands the artificial muscle. The muscle contracts when the charge is removed and flattens the shape of the sling, blinking the eye. When the charge is reactivated, the muscle relaxes and the soft center reverts back to its original shape.

“The amount of force and movement the artificial muscle generates is very similar to natural muscle,” Tollefson said. An implanted battery source similar to those used in cochlear implants would power the artificial muscle.

For patients who have one functioning eyelid, a sensor wire threaded over the normal eyelid could detect the natural blink impulse and fire the artificial muscle at the same time. Among patients lacking control of either eyelid, an electronic pacemaker similar to those used to regulate heartbeats could blink the eye at a steady rate, and be deactivated by a magnetic switch.

The researchers are now refining the technique on cadavers and animal modes. They estimate the technology will be available for patients within the next five years.

New visual pathway linked to photophobia in migraines identified

Sun, 10 Jan 2010 14:41:43 PST

( from http://www.rxpgnews.com ) Ask anyone who suffers from migraine headaches what they do when they're having an attack, and you're likely to hear "go into a dark room." And although it's long been known that light makes migraines worse, the reason why has been unclear.

Now scientists at Beth Israel Deaconess Medical Center (BIDMC) have identified a new visual pathway that underlies sensitivity to light during migraine in both blind individuals and in individuals with normal eyesight. The findings, which appear today in the Advance On-line issue of Nature Neuroscience, help explain the mechanism behind this widespread condition.

A one-sided, throbbing headache associated with a number of symptoms, including nausea, vomiting, and fatigue, migraines are notoriously debilitating and surprisingly widespread, affecting more than 30 million individuals in the U.S. alone. Migraine pain is believed to develop when the meninges, the system of membranes surrounding the brain and central nervous system, becomes irritated, which stimulates pain receptors and triggers a series of events that lead to the prolonged activation of groups of sensory neurons.

"This explains the throbbing headache and accompanying scalp and neck-muscle tenderness experienced by many migraine patients," explains the study's senior author Rami Burstein, PhD, Professor of Anesthesia and Critical Care Medicine at BIDMC and Harvard Medical School.

In addition, for reasons that were unknown, nearly 85 percent of migraine patients are also extremely sensitive to light, a condition known as photophobia.

"Migraine patients may wear sunglasses, even at night," he notes, adding that the dimmest of light can make migraine pain worse. Extremely disabling, photophobia prevents patients from such routine activities as reading, writing, working or driving.

It was the observation that even blind individuals who suffer from migraines were experiencing photophobia that led Burstein and first author Rodrigo Noseda, PhD, to hypothesize that signals transmitted from the retina via the optic nerve were somehow triggering the intensification of pain.

The investigators studied two groups of blind individuals who suffer migraine headaches. Patients in the first group were totally blind due to eye diseases such as retinal cancer and glaucoma; they were unable to see images or to sense light and therefore could not maintain normal sleep-wake cycles. Patients in the second group were legally blind due to retinal degenerative diseases such as retinitis pigmentosa; although they were unable to perceive images, they could detect the presence of light and maintain normal sleep-wake cycles.

"While the patients in the first group did not experience any worsening of their headaches from light exposure, the patients in the second group clearly described intensified pain when they were exposed to light, in particular blue or gray wavelengths," explains Burstein. "This suggested to us that the mechanism of photophobia must involve the optic nerve, because in totally blind individuals, the optic nerve does not carry light signals to the brain.

"We also suspected that a group of recently discovered retinal cells containing melanopsin photoreceptors [which help control biological functions including sleep and wakefulness] is critically involved in this process, because these are the only functioning light receptors left among patients who are legally blind."

The scientists took these ideas to the laboratory, where they performed a series of experiments in an animal model of migraine. After injecting dyes into the eye, they traced the path of the melanopsin retinal cells through the optic nerve to the brain, where they found a group of neurons that become electrically active during migraine.

"When small electrodes were inserted into these 'migraine neurons,' we discovered that light was triggering a flow of electrical signals that was converging on these very cells," says Burstein. "This increased their activity within seconds."

And even when the light was removed, he notes, these neurons remained activated. "This helps explain why patients say that their headache intensifies within seconds after exposure to light, and improves 20 to 30 minutes after being in the dark."

The discovery of this pathway provides scientists with a new avenue to follow in working to address the problem of photophobia.

"Clinically, this research sets the stage for identifying ways to block the pathway so that migraine patients can endure light without pain," adds Burstein.

Dystroglycan- potential therapy to treat congenital muscular dystrophies

Fri, 01 Jan 2010 11:14:49 PST

( from http://www.rxpgnews.com ) With the discovery of a new type of chemical modification on an important muscle protein, a University of Iowa study improves understanding of certain muscular dystrophies and could potentially lead to new treatments for the conditions.

The findings, which appear in the Jan. 1, 2010, issue of the journal Science, may also have implications for detecting metastasizing cancer cells.

After they are initially made, most proteins are modified through the addition of sugar chains, fats or other chemical groups. These modifications can completely change how a protein works and where it is located in the body. Disruption of these modifications can alter protein function, too, and can lead to disease.

The UI study focused on dystroglycan, a cell membrane protein that is disrupted in many forms of muscular dystrophy. Normal dystroglycan is modified with a unique sugar chain that allows the protein to "glue" muscle membranes to the basal lamina -- a tough layer of extracellular proteins. This arrangement reinforces the fragile muscle membrane and prevents small tears that occur naturally from expanding and damaging the membrane.

Recent work, including studies by the UI team, show that disrupting dystroglycan's ability to attach to the basal lamina causes congenital muscular dystrophies and also leads to cancer progression in epithelial cell cancer. In these conditions, the dystroglycan sugar chain is incompletely or incorrectly assembled and the dystroglycan cannot bind tightly to laminin.

"Dystroglycan is a complex and unusual glycoprotein. It is heavily covered with many types of sugars. We wanted to know the shape and make up of the unique sugar chain that allows dystroglycan to bind to laminin," said study leader Kevin Campbell, Ph.D., professor and head of molecular physiology and biophysics at the UI Roy J. and Lucille A. Carver College of Medicine and a Howard Hughes Medical Institute investigator.

Lead study author Takako Yoshida-Moriguchi, Ph.D., a postdoctoral researcher in Campbell's lab, used a combination of biochemical methods and chemical and structure analysis to determine that a critical link within the sugar chain involves a phosphate group. This type of link is found in yeast and fungi but has not previously been found in higher organisms like mammals.

"This phosphate link is very unusual, which may explain why the actual structure of dystroglycan's laminin-binding sugar chain has been a mystery for many years despite the efforts of numerous research teams," said Campbell, who also holds the Roy J. Carver Chair of Physiology and Biophysics. "The findings help explain what is happening in congenital muscular dystrophies where the dystroglycan sugar chain is truncated and ends at the phosphate. The bare phosphate does not bind laminin; it has to be further modified."

Several enzymes are involved in building the sugar chain beyond the phosphate, and mutations in these enzymes are the cause of congenital muscular dystrophies.

"If we can discover the entire structure and make up of the sugar chain beyond the phosphate link, we might be able to target some of the enzymes involved in building the sugar chain, and thus, develop therapies to treat congenital muscular dystrophies," Campbell said.

In certain cancer cells, one of these enzymes, known as LARGE, also is suppressed. Campbell speculated that loss of LARGE activity produces dystroglycan that is unable to interact with the basal lamina, which makes the cancer cells more mobile and allows them to escape into the bloodstream. The study's findings could lead to new methods for tracking metastasizing cancer cells.

Members of the European Parliament discuss achieving heart health in Europe

Wed, 09 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Brussels, 9 December 2009 - Members of the European Parliament Heart Group (MEP HG) meet today, in Brussels, with the Cardiology profession and representatives of national Heart Foundations to evaluate the achievements at EU level in combating Cardiovascular Disease (CVD), and to reveal the need for further action.

With the title 'Achieving Heart Health in Europe: Why the European Parliament Matters', the meeting is the first since the European elections in June this year. During the 2004-2009 term, the MEP Heart Group was the largest forum on health in the European Parliament. The group resumes now its activities which endeavour to raise heart health as a priority on the EU political agenda. CVD is the number one killer in Europe, accounting for over 2 million deaths in the EU alone and costing the EU over 190 billion Euros each year. (1)

Mr Dirk Sterckx MEP, Co-chair of the MEP HG, believes that the European Union has a major role to play in fostering heart health promotion and developing wide-ranging prevention strategies. The European Parliament has set the example with the 2007 Resolution on action to tackle cardiovascular disease (2). However, the recent declining trends in CVD deaths in Europe are now slowing down. This is very worrying; it represents an alarm call to the European Commission and the Council.

The EU cannot turn its back on CVD, agrees Linda McAvan MEP, Co-chair of the MEP HG. Evidence does exist that prevention brings significant health gains. It is therefore the task of decision makers at European and national level to ensure that effective policies supporting prevention are put in place.

CVD is currently THE public health challenge in Europe, says Prof. Simon Capewell, Professor of Clinical Epidemiology, Liverpool University, UK. There are widening gaps both between and within Member States. CVD mortality rates have been decreasing in the past 30 years but they are now flattening. This is extremely frustrating because 80% of premature CVD deaths can be prevented by tackling the major risk factors, diet and smoking. A comprehensive European heart health strategy addressing health promotion and disease prevention is a moral responsibility for policymakers.

Significant policy developments addressing cardiovascular disease have taken place in Europe in the last decade. These include the Council Conclusions to promote heart health (adopted in 2004), the European Heart Health Charter (launched in 2007), and the European Parliament Resolution on action to tackle cardiovascular disease (adopted with a large majority in July 2007). Despite this, a tangible European strategy to address CVD is still non-existent. The MEP HG is calling for action from the European Commission and Member States to fill the gap. We urgently need to address what should be the Number 1 public health priority in Europe.

UC Berkeley social scientists build case for 'survival of the kindest'

Tue, 08 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Researchers at UC Berkeley are challenging long-held beliefs that human beings are wired to be selfish. In a wide range of studies, social scientists are amassing a growing body of evidence to show we are evolving to become more compassionate and collaborative in our quest to survive and thrive.

In contrast to every man for himself interpretations of Charles Darwin's theory of evolution by natural selection, Dacher Keltner, a UC Berkeley psychologist and author of Born to be Good: The Science of a Meaningful Life, and his fellow social scientists are building the case that humans are successful as a species precisely because of our nurturing, altruistic and compassionate traits.

They call it survival of the kindest.

Because of our very vulnerable offspring, the fundamental task for human survival and gene replication is to take care of others, said Keltner, co-director of UC Berkeley's Greater Good Science Center. Human beings have survived as a species because we have evolved the capacities to care for those in need and to cooperate. As Darwin long ago surmised, sympathy is our strongest instinct.

Keltner's team is looking into how the human capacity to care and cooperate is wired into particular regions of the brain and nervous system. One recent study found compelling evidence that many of us are genetically predisposed to be empathetic.

The study, led by UC Berkeley graduate student Laura Saslow and Sarina Rodrigues of Oregon State University, found that people with a particular variation of the oxytocin gene receptor are more adept at reading the emotional state of others, and get less stressed out under tense circumstances.

Informally known as the cuddle hormone, oxytocin is secreted into the bloodstream and the brain, where it promotes social interaction, nurturing and romantic love, among other functions.

The tendency to be more empathetic may be influenced by a single gene, Rodrigues said.

While studies show that bonding and making social connections can make for a healthier, more meaningful life, the larger question some UC Berkeley researchers are asking is, How do these traits ensure our survival and raise our status among our peers?

One answer, according to UC Berkeley social psychologist and sociologist Robb Willer, is that the more generous we are, the more respect and influence we wield. In one recent study, Willer and his team gave participants each a modest amount of cash and directed them to play games of varying complexity that would benefit the public good. The results, published in the journal American Sociological Review, showed that participants who acted more generously received more gifts, respect and cooperation from their peers and wielded more influence over them.

The findings suggest that anyone who acts only in his or her narrow self-interest will be shunned, disrespected, even hated, Willer said. But those who behave generously with others are held in high esteem by their peers and thus rise in status.

Given how much is to be gained through generosity, social scientists increasingly wonder less why people are ever generous and more why they are ever selfish, he added.

Such results validate the findings of such positive psychology pioneers as Martin Seligman, a professor at the University of Pennsylvania whose research in the early 1990s shifted away from mental illness and dysfunction, delving instead into the mysteries of human resilience and optimism.

While much of the positive psychology being studied around the nation is focused on personal fulfillment and happiness, UC Berkeley researchers have narrowed their investigation into how it contributes to the greater societal good.

One outcome is the campus's Greater Good Science Center, a West Coast magnet for research on gratitude, compassion, altruism, awe and positive parenting, whose benefactors include the Metanexus Institute, Tom and Ruth Ann Hornaday and the Quality of Life Foundation.

Christine Carter, executive director of the Greater Good Science Center, is creator of the Science for Raising Happy Kids Web site, whose goal, among other things, is to assist in and promote the rearing of emotionally literate children. Carter translates rigorous research into practical parenting advice. She says many parents are turning away from materialistic or competitive activities, and rethinking what will bring their families true happiness and well-being.

I've found that parents who start consciously cultivating gratitude and generosity in their children quickly see how much happier and more resilient their children become, said Carter, author of Raising Happiness: 10 Simple Steps for More Joyful Kids and Happier Parents which will be in bookstores in February 2010. What is often surprising to parents is how much happier they themselves also become.

As for college-goers, UC Berkeley psychologist Rodolfo Mendoza-Denton has found that cross-racial and cross-ethnic friendships can improve the social and academic experience on campuses. In one set of findings, published in the Journal of Personality and Social Psychology, he found that the cortisol levels of both white and Latino students dropped as they got to know each over a series of one-on-one get-togethers. Cortisol is a hormone triggered by stress and anxiety.

Meanwhile, in their investigation of the neurobiological roots of positive emotions, Keltner and his team are zeroing in on the aforementioned oxytocin as well as the vagus nerve, a uniquely mammalian system that connects to all the body's organs and regulates heart rate and breathing.

Both the vagus nerve and oxytocin play a role in communicating and calming. In one UC Berkeley study, for example, two people separated by a barrier took turns trying to communicate emotions to one another by touching one other through a hole in the barrier. For the most part, participants were able to successfully communicate sympathy, love and gratitude and even assuage major anxiety.

Researchers were able to see from activity in the threat response region of the brain that many of the female participants grew anxious as they waited to be touched. However, as soon as they felt a sympathetic touch, the vagus nerve was activated and oxytocin was released, calming them immediately.

Sympathy is indeed wired into our brains and bodies; and it spreads from one person to another through touch, Keltner said.

The same goes for smaller mammals. UC Berkeley psychologist Darlene Francis and Michael Meaney, a professor of biological psychiatry and neurology at McGill University, found that rat pups whose mothers licked, groomed and generally nurtured them showed reduced levels of stress hormones, including cortisol, and had generally more robust immune systems.

Overall, these and other findings at UC Berkeley challenge the assumption that nice guys finish last, and instead support the hypothesis that humans, if adequately nurtured and supported, tend to err on the side of compassion.

This new science of altruism and the physiological underpinnings of compassion is finally catching up with Darwin's observations nearly 130 years ago, that sympathy is our strongest instinct, Keltner said.

Migraine raises risk of most common form of stroke

Mon, 16 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Pooling results from 21 studies, involving 622,381 men and women, researchers at Johns Hopkins have affirmed that migraine headaches are associated with more than twofold higher chances of the most common kind of stroke: those occurring when blood supply to the brain is suddenly cut off by the buildup of plaque or a blood clot.

The risk for those with migraines is 2.3 times those without, according to calculations from the Johns Hopkins team, to be presented Nov. 16 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando. For those who experience aura, the sighting of flashing lights, zigzag lines and blurred side vision along with migraines, the risk of so-called ischemic stroke is 2.5 times higher, and in women, 2.9 times as high.

Study participants, mostly in North America and Europe, were between the ages 18 and 70, and none had suffered a stroke prior to enrollment.

Senior study investigator and cardiologist Saman Nazarian, M.D., says the team's latest analysis, believed to be the largest study of its kind on the topic, reinforces the relationship between migraine and stroke while correcting some discrepancies in previous analyses. For examples, a smaller combination study in 2005 by researchers in Montreal showed a bare doubling of risk, yet mixed together different mathematical measures of risk, while the Hopkins study kept them separate, pooling together only like measures. As well, another half dozen recent and smaller studies from Harvard University yielded mixed results, some showing a link between migraines and ischemic stroke, while one did not show a tie-in.

Nazarian says that while nearly 1,800 articles have been written about the relationship between migraine and ischemic stroke, the Hopkins review was more selective, combining only studies with similar designs and similar groups of people, and more comprehensive, including analysis of unpublished data.

Identifying people at highest risk is crucial to preventing disabling strokes, says Nazarian, an assistant professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. Based on this data, physicians should consider addressing stroke risk factors in patients with a history or signs of light flashes and blurry vision associated with severe headaches.

Prevention and treatment options for migraine, he says, range from smoking cessation and taking anti-blood pressure or blood-thinning medications, such as aspirin. In women with migraines, stopping use of oral contraceptives or hormone replacement therapy may be recommended.

Such widespread use of hormone-controlling drugs is what Nazarian says may explain why women with migraines have such high risk of ischemic stroke. Contraceptives and other estrogen therapies are both known to contribute to long-term risk factors for cardiovascular diseases and stroke, such as high blood pressure and increased reactivity by clot-forming blood platelets.

Nazarian says the researchers' next steps are to evaluate if preventive therapies, especially aspirin, offset the risk of ischemic stroke in people with migraines.

Women and cardiovascular health conference to highlight need for gender-specific research

Fri, 30 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The 'Red Alert for Women's Hearts' conference, taking place on 5 November 2009, at the European Heart House, Sophia Antipolis, France, will address the subject of Women and CVD. The conference is jointly organised by the European Society of Cardiology (ESC) and European Heart Network (EHN), as part of Work Package 6 of the EuroHeart project (1).

Heart disease and stroke are the leading causes of death for women worldwide, killing more than 8.6 million, more than the total number who die from cancer, tuberculosis, HIV/AIDS and malaria combined.

However, the risk for women is largely under-estimated, by both the general population and often by the medical profession itself. This is due to the fact that women usually suffer from CVD 10 years later in their life than men: the risk increases after menopause, partly because of ovarian hormone deficiency that favours hypertension, diabetes, hyperlipidemia, central obesity and the metabolic syndrome.

In the report that will be presented at the conference (2), Professor Stramba Badiale, MD, PhD at the Department of Rehabilitation Medicine, IRCCS Istituto Auxologico Italiano, finds that women are underrepresented in cardiovascular research in Europe. In the 62 randomized clinical trials published between 2006 and July 2009, only 33.5% of enrolled participants were women, he says.

This underrepresentation is particularly noticeable in the fields of cholesterol-lowering therapy, ischaemic heart disease and heart failure.

Professor Roberto Ferrari, President of the ESC says: With regard to cardiovascular health, we do lack data for women simply because the majority of clinical trials are conducted on men. It is important to have special clinical trials conducted only on women because their cardiovascular pathology is, at least at some point during their lives, different from that of men and it is incorrect to apply data derived from studies on men to women.

Another finding of the report that supports the conference programme is that only 50% of the clinical trials conducted in the last three years which enrolled both men and women reported the analysis of the results by gender.

Susanne Logstrup, director of the EHN, regrets that, as a result, safety and efficacy of several drugs have been evaluated predominantly in male populations.

Professor Stramba-Badiale is hopeful that the report and the conference will encourage new practice amongst the research community, with a systematic enrolment of women in clinical trials. New data should improve the clinical management of CVD and, in the future, develop possible gender specific diagnostic and therapeutic strategies, he says.

The research is part of the EuroHeart project, which aims at defining areas of policies and public health interventions which can contribute to prevent avoidable deaths and disability across Europe. It is led by the ESC, in partnership with the EHN, and is co-funded by the European Commission Public Health Programme 2003-2008.

The 'Red alert for women's hearts' conference will systematically review the place of women in all aspects of scientific literature, whether clinical trials, guidelines, medical curriculum or regulatory processes.

More than 60 awareness campaigns addressing the particular issue of women and cardiovascular diseases have been organised in the last 20 years in the 19 countries participating in WP 6 of the EuroHeart project. This is evidence that national Heart Foundations and Cardiac Societies have long been aware of the urgent need to promote the issue amongst the female population and health professionals. The results of campaigns showed an increased awareness that cardiovascular diseases are the leading cause of death for women. Despite this, gender-specific training for cardiologists is still lacking in the majority of European countries.

The objective of this conference is to create a series of recommendations for policy makers, research funding agencies and regulatory entities, at both national and EU level.

Red Alert for Women's Hearts is also the opportunity to look at how countries address the lack of information of the population and of health professionals, by giving an overview of past campaigns and their impact, country by country.

NHLBI to convene symposium on cardiovascular regenerative medicine

Thu, 08 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) With advancements in the field of stem cell research accelerating, the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) will hold its third Symposium on Cardiovascular Regenerative Medicine to review the latest findings in the field and examine future directions. The symposium will include a discussion on ways to move promising findings in the laboratory into clinical trials, in hopes of speeding stem cell-related treatments to patients.

The event will be held Oct. 14 -15 at the Natcher Conference Center on the NIH campus in Bethesda, Md.

This symposium will help us move forward to spur new scientific efforts that will advance the field of cardiovascular stem cell research, said NHLBI Director Elizabeth G. Nabel, M.D., who will deliver the keynote address on the NHLBI Roadmap for stem cell research. With more than 16 million Americans living with damage to heart muscles or blood vessels due to heart attacks, this area of research holds great promise to improve lives.

Nabel noted that the theme of the symposium coincides with the NHLBI's recent funding of stem cell research projects under the American Recovery and Reinvestment Act. The NHLBI has made stem cell research a Signature Project under the Recovery Act and is putting a priority on funding research that could lead to the development of regenerative treatment for heart, lung, and blood diseases, added Nabel.

Some symposium sessions will focus on cardiac development and how epithelial cells transform into mesenchymal cells, a process which is related to organ development and some fibrotic diseases. Another session will review recent advances, and future potential, for embryonic stem cells and induced pluripotent stem (iPS) cells that could be used for cell therapy in the heart. IPS cells are artificially derived stem cells that can give rise to any fetal or adult cell type. The symposium will also feature a series of talks related to the NHLBI's newly launched Progenitor Cell Biology Consortium, whose 18 teams of scientists are developing the field of stem and progenitor cell tools and therapies.

Stem cell experts from the United States, Canada, the Netherlands, Spain, and Sweden are scheduled to speak, and the symposium will also include a number of poster sessions. Among the highlights of the scheduled list of speakers:

George Q. Daley, M.D., Ph.D., Harvard Medical School/Children's Hospital of Boston. Modeling Blood Disease with iPS Cells. Wednesday, Oct. 14, 8:35 a.m. Daley will discuss ways to use induced pluripotent stem cells to model blood disease. This line of research could provide new targets for drug therapy.

Bernhard Kuhn, M.D., Harvard Medical School/Children's Hospital of Boston, Stimulating Myocardial Regeneration with Cardiomyocyte Proliferation Factors. Thursday, Oct. 15, 11 a.m. Kuhn will discuss ways to recruit existing heart tissue into producing new cells, which could help repair heart damage following heart attack or stroke.

Jonas Frisen, M.D., Ph.D., Karolinska Institute, Sweden, Cardiomyocyte Renewal in Humans. Thursday, Oct. 15, 11:20 a.m. Frisen will discuss his work using residual atmospheric radiation remaining from aboveground atomic bomb testing in the 1960s from sites around the world to determine the age of cardiomyocytes, or cardiac muscle cells, in humans. Until now, it has been difficult to determine the age of cells in the heart, so there was little information about whether new tissue was being generated in the heart. Frisen's research suggests that a tiny fraction of tissue cells within the heart are new cardiomyocytes, a finding which could lead to new ways to encourage more such tissue growth.

Life and death in the living brain

Mon, 10 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Like clockwork, brain regions in many songbird species expand and shrink seasonally in response to hormones. Now, for the first time, University of Washington neurobiologists have interrupted this natural annual remodeling of the brain and have shown that there is a direct link between the death of old neurons and their replacement by newly born ones in a living vertebrate.

The scientists introduced a chemical into one side of sparrow brains in an area that helps control singing behavior to halt apoptosis, a cell suicide program. Twenty days after introduction of the hormones the researchers found that there were 48 percent fewer new neurons than there were in the side of the brain that did not receive the cell suicide inhibitor.

This is the first demonstration that if you decrease apoptosis you also decrease the number of new brain cells in a live animal. The next step is to understand this process at the molecular level, said Eliot Brenowitz, a UW professor of psychology and biology and co-author of a new study. His co-author is Christopher Thompson, who earned his doctorate at the UW and is now at the Free University of Berlin.

The seasonal hormonal drop in birds may mimic what is an age-related drop in human hormone levels. Here we have a bird model that is natural and maybe similar genes have a similar function in humans with degenerative diseases such as Alzheimer's and Parkinson's, as well as strokes, which are associated with neuron death.

The research involved Gambel's white-crowned sparrows, a songbird subspecies that winters in California and migrates to Alaska in the spring and summer to breed and raise its young. The sparrow's brain regions, including one called the HVC, which control learned song behavior in males, expand and shrink seasonally. Thompson and Brenowitz previously found that neurons in the HVC begin dying within four days hours after the steroid hormone testosterone is withdrawn from the bird's brains. Thousands of neurons died over this time.

In the new work, the UW researchers received federal and state permission to capture 10 of the sparrows in Eastern Washington at the end of the breeding season. After housing the birds for three months, they castrated the sparrows and then artificially brought them to breeding condition by implanting testosterone and housing them under the same long-day lighting conditions that they would naturally be exposed to in Alaska. This induced full growth of the song control system in the birds' brains.

Next the researchers transitioned the birds to a non-breeding condition by reducing the amount of light they were exposed to and removing the implanted testosterone. They infused the HVC on one side of the brain with chemicals, called caspase inhibitors, that block apoptosis, and two chemical markers that highlight mature and new neurons. Twenty days later the birds were euthanized and sections of their brains were examined under a microscope.

These procedures were done with the approval of the UW's Institutional Animal Care and Use Committee and the National Institute of Mental Health. The latter funded the research.

The HVC straddles both hemispheres of the brain but the two sides are not directly connected. When Thompson counted the number of newly born neurons that had migrated to the HVC, he found only several hundred of them among the hundreds of thousands of mature neurons he examined. And there were nearly half the number of new neurons in the side of the HVC where brain cell death was inhibited compared with the other, untreated side of the HVC. This shows there is some direct link between the death of old neurons and the addition of new cells that were born elsewhere in the brain and have migrated, said Brenowitz. What allows new cells to be incorporated into the brain is the big question. This is particularly true on a molecular level where we want to know what is the connection between cell death and neurogenesis and which genes are responsible.

Salamanders can regenerate damaged lungs

Sat, 08 Aug 2009 14:19:15 PST

( from http://www.rxpgnews.com ) The salamander is a super hero of regeneration, able to replace lost limbs, damaged lungs, sliced spinal cord - even bits of lopped-off brain.

But it turns out that this remarkable ability isn't so mysterious after all - suggesting that researchers could learn how to replicate it in people.

Scientists had long credited the diminutive amphibious creature's outsized capabilities to 'pluripotent' cells that, like human embryonic stem cells, have the uncanny ability to morph into whatever appendage, organ or tissue happens to be needed or is due for a replacement.

But a team of seven researchers, including a University of Florida - zoologist, debunk that notion.

Based on experiments on genetically modified axolotl salamanders, the researchers have shown that cells from the salamander's different tissues retain the 'memory' of those tissues when they regenerate, contributing with few exceptions only to the same type of tissue from where they came.

Standard mammal stem cells operate the same way, albeit with far less dramatic results - they can heal wounds or knit bone together, but not regenerate a limb or rebuild a spinal cord.

What's exciting about the new findings is they suggest that harnessing the salamander's regenerative wonders is at least within the realm of possibility for human medical science.

Also, the salamanders heal perfectly, without any scars whatsoever, another ability people would like to learn how to mimic, said Malcolm Maden, professor of biology and author of the paper.

Axolotl salamanders, originally native to only one lake in central Mexico, are evolutionary oddities that become sexually reproducing adults while still in their larval stage.

When an axolotl loses, for example, a leg, a small bump called a blastema forms over the injury. It takes only about three weeks for this blastema to transform into a new, fully functioning replacement leg - not long considering these animals can live 12 or more years.

These findings appeared in the Thursday edition of Nature.

Smoking associated with rapid progression of multiple sclerosis

Mon, 13 Jul 2009 15:31:39 PST

( from http://www.rxpgnews.com ) Patients with multiple sclerosis who smoke appear to experience a more rapid progression of their disease, according to a report in the July issue of Archives of Neurology, one of the JAMA/Archives journals.

Cigarette smokers are at higher risk of developing multiple sclerosis (MS), according to background information in the article. However, the effect of smoking on the progression of MS remains uncertain.

Brian C. Healy, Ph.D., of Brigham and Women's Hospital, Harvard Medical School and Massachusetts General Hospital, Boston, and colleagues studied 1,465 patients with MS who visited a referral center between February 2006 and August 2007. Participants had an average age of 42 and had MS for an average of 9.4 years. Their progression was assessed by clinical characteristics as well as by magnetic resonance imaging (MRI) over an average of 3.29 years.

A total of 780 (53.2 percent) of the patients had never smoked, 428 (29.2 percent) had smoked in the past and 257 (17.5 percent) were current smokers. During follow-up, seven never-smokers began smoking and 57 current smokers quit. Current smokers had significantly more severe disease at the beginning of the study in terms of scores on disability scales and also in the analysis of MRI factors. Current smokers were also more likely to have primary progressive MS, characterized by a steady decline, rather than relapsing-remitting MS (involving alternating periods of attacks and symptom-free periods).

A group of 891 patients was assessed over time to evaluate the rate of conversion from relapsing-remitting MS to secondary progressive MS (steady decline that develops after a period of relapsing-remitting symptoms). During an average of 3.34 years, 72 patients (20 of 154 smokers, 20 of 237 ex-smokers, and 32 of 500 never-smokers) experienced this progression. "The conversion from relapsing-remitting MS to secondary progressive MS occurred faster in current smokers compared with never-smokers but was similar in ex-smokers and never-smokers," the authors write.

An adverse effect of smoking on the progression of MS would be consistent with previous research, the authors note. Components of cigarette smoke are known to have toxic effects on brain and neural tissue; for example, cyanides, which have been associated with the destruction of nerve cells' myelin coating (a characteristic feature of MS) in animals. "Other chemicals in smoke (e.g., nicotine) can compromise the blood-brain barrier or have immunomodulatory effects," the authors write. "Cigarette smoke increases the frequency and duration of respiratory infections, which have been linked to risk of MS and to the occurrence of MS relapses."

"In conclusion, the results of this large and in part prospective investigation support the hypothesis that cigarette smoking has an adverse effect on progression of MS as measured by clinical and MRI outcomes," they conclude. "Although causality remains to be proved, these findings suggest that patients with MS who quit smoking may not only reduce their risk of smoking-related diseases but also delay the progression of MS."

New research to reduce drug side-effects

Fri, 10 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) They are a group of drugs which millions of people rely on to keep pain at bay but they can have unwanted side-effects which are sometimes more serious than the original health problem. Now scientists at The University of Nottingham are taking part in the largest-ever study on the safety of Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) that has ever been performed.

The project is called SOS (Safety Of non-Steroidal anti-inflammatory drugs) and will study the medical information of 35 million people in Europe to assess the incidence and nature of harmful side-effects on the cardiovascular and gastrointestinal systems of patients. It's hoped the results will lead to better guidance for doctors on how to balance the advantages of prescribing the drugs with the associated risks of heart and digestive problems.

NSAIDS are widely used in medicine for treating pain, inflammation and degenerative diseases like arthritis. The most commonly-used are aspirin and ibuprofen. But their use is associated with an increased risk of minor and serious gastrointestinal complications. It's estimated that there are thousands of these cases in the European Union every year. Prompted by these problems, a new class of NSAIDS called 'Coxibs' have been developed to reduce the risk of this type of side-effect, but the use of these new drugs has since been linked with an increased risk of heart problems such as heart attack and stroke.

Clinicians and scientists now agree that the risk of stomach problems has to be balanced against the risk of cardiovascular interference. Both risks may differ in one person and for the 30 different types of NSAIDS available in the EU. Up to now research studies have been too small to be effective in terms of providing decision models for doctors and drug regulators but it's hoped this new large survey will result in a much more accurate prescription method to minimize drug-related harm.

Over the next two and a half years, published literature on previous clinical trials and observational studies will be scrutinized to identify any methodological inconsistencies and knowledge gaps and this information will be used to design and carry out an EU-wide observational study. This study will be the biggest of its kind ever undertaken in this field. It will include data from more than 35 million Europeans, taken from existing healthcare databases in the UK, the Netherlands, Germany and Italy. The researchers will use the data to create a variety of decision models to help doctors prescribe the most suitable type of NSAID for a particular patient and lower the risk of unwanted gastrointestinal or cardiovascular side-effects.

The University of Nottingham is working with ten other leading European research institutions on the three-year project which is being funded with a 2.8 million Euros grant from the EC's 7th Framework Programme. Fundamental to the project is QResearch, a not-for-profit partnership between The University of Nottingham and leading primary care system supplier EMIS, which uses data collected over the past 17 years.

Professor of Clinical Epidemiology and General Practice, Julia Hippisley-Cox, who founded QResearch, said: The SOS project will help quantify and compare the risks of different NSAIDs based on an individual's profile and should help lead patients and doctors make better decisions regarding treatment options.

New research to reduce drug side-effects

Fri, 10 Jul 2009 03:59:36 PST

EUROPACE raises remote monitoring profile

Sun, 21 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Moving to a more continuous follow-up approach would have the tremendous advantages of enhancing patient safety, decreasing physician and nurse work load, and allowing health staff to focus on medical emergencies, urged Professor Angelo Auricchio, from the European Heart Rhythm Association (EHRA) and official spokesperson of the European Society of Cardiology (ESC), adding that such systems may have the additional advantage of being more cost effective for health care providers.

Currently only around 1 % of patients in Europe with implantable cardiac devices are being monitored with remote devices, the majority are still being followed up by routine face to face clinic visits. Despite wide availability of remote monitoring in many European countries, few countries offer patients such systems. Even in countries that have introduced remote monitoring there are widespread disparities between centres, added Professor Auricchio, who works at the Cardiocentre Ticino (Lugano, Switzerland).

Cardiovascular implantable electronic devices (CIEDs) - which include cardiac pacemakers, implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy (CRT) devices, implantable cardiovascular monitors and implantable loop recorders - have now been developed with numerous programmable features allowing for storage of substantial amounts of diagnostic information.

The European Heart Rhythm Association (EHRA) and Heart Rhythm Society (HRS) expert consensus on monitoring of cardiovascular electronic devices, published last year, estimated that in 2006 approximately 250,000 pacemakers and 50,000 ICDs were implanted in Europe (1). The numbers implanted are estimated to be increasing by 5 to 10 % per year. What has become increasingly apparent, explained Professor Auricchio, is that once the device has been implanted, it needs to be followed up effectively to allow it to work efficiently.

This means that more than two million follow-up encounters with device patients are now needed in Europe each year, which is pushing the health care system to breaking point. Services are so overstretched by routine follow ups that they do not have much spare capacity to deal with emergencies when they come in, said Professor Auricchio.

The solution, suggests Professor Auricchio, is to increase the number of devices that can be interrogated remotely. Technology is available to download data related to device function, arrhythmia frequency, cardiovascular hemodynamic parameters and patient activity, from specific CIEDs and transmit the encrypted data using telephone technology to remote-secure monitoring centres. Here health care staff can both identify errant device behaviour, as well as patient's physiological response to a multitude of programmable therapies.

There are many advantages for remote devices. With the current face to face visit approach, physicians commonly first learn about critical device malfunctions and physiological changes when the patient returns to the clinic for a regular scheduled follow-up and manual device interrogation, which only takes place two to four times per year, depending on the patient status. With remote monitoring, problems can be identified immediately.

Continuous control of the device will permit detection of possible device dysfunction at a very early stage which allows us to take immediate action, thus improving patient safety significantly. said Professor Josep Brugada, President of the EHRA.

The European Heart Rhythm Association (EHRA) and Heart Rhythm Society (HRS) expert consensus document, which set out to determine what was needed to provide appropriate levels of care, concluded: Globalization and new Internet-based technologies for monitoring CIEDs are imposing new rules for patient data management and data-sharing. Competent authorities, national ministries of health, and patient organizations need to find practical and easy solutions for physicians to have rapid and complete access to device relevant data for delivering the most appropriate therapy.

The document adds that payers and regulators need to improve their recognition of the importance of CIED follow-up and develop adequate reimbursement strategies. There is no point investing in the device without comparable investment in the long-term follow-up and therapy! write the authors.

To understand the new models of reimbursement, EHRA in conjunction with Eucomed, now plans to survey the costs involved with in hospital CIED follow-up throughout Europe. In addition to the direct medical costs the survey will also include indirect costs, such as those involved in relatives accompanying patients on hospital visits. We need to have a better idea of the baseline costs so that we can start to understand the cost efficiency of introducing remote monitoring, said Professor Auricchio.

Brain protein BDNF might get you hooked on drugs, alcohol

Wed, 17 Jun 2009 14:23:35 PST

( from http://www.rxpgnews.com ) A brain protein can practically hook you on to drugs and alcohol by hijacking the normal functioning of its reward circuitry.

Researchers investigating this addiction 'switch' have now implicated a naturally occurring protein, a dose of which allowed them to get rats hooked with no drugs at all.

Chronic drug users, as noted by previous research, can experience an increase in this protein called BDNF - in the brain's reward circuitry.

Researchers noted that a single injection of BDNF made rats behave as though they were dependent on opiates -.

Though rats instinctively prefer certain smells, lighting and texture, these rats left their comfort zone in search of a fix.

'If we can understand how the brain's circuitry changes in association with drug abuse, it could potentially suggest ways to medically counteract the effects of dependency,' said Scott Steffensen, neuroscientist at Brigham Young University -.

He co-authored the study with two of his undergraduate students, one of his graduate students, and a team of researchers at the University of Toronto, said a BYU release.

'This work may reveal a mechanism that underlies drug addiction,' said study co-author Hector Vargas-Perez, a Toronto neurobiologist.

The study was published in Science.

Nerve cells permit brain to regenerate itself with Activin A

Tue, 09 Jun 2009 15:19:33 PST

( from http://www.rxpgnews.com ) Nerve cells in the brain produce an anti-inflammatory molecule that allows the brain to repair itself, according to a new study.

Inflammation is the response of body tissues to injury or irritation -- characterized by pain, swelling, redness and heat.

New findings throw light on how the brain heals itself and may change the way we think about treating chronic neuro-degenerative diseases like Parkinson's and Alzheimer's.

Discovery of the brain's capacity to regenerate is very recent. Neural stem cells were first discovered in the brain in the early 1990s, but it took scientists a further 10 years to show that they can regenerate nerve cells in the brain.

'Given that we now know regeneration can occur, we want to understand what drives it and what blocks it, particularly in diseases like Parkinson's and Alzheimer's,' said Bryce Vissel, neuroscientist at the Garvan Institute of Medical Research -, Australia.

'We triggered rapid neuro-degeneration in the brains of mice, and it was immediately followed by a very rapid regenerative response. We wanted to know why this response could occur so effectively after acute neuro-degeneration,' he said.

'On further investigation, we found high levels of a molecule known as Activin A whenever regeneration occurred. This was especially interesting because Activin A is released from nerve cells.

'Clearly Activin A was playing an important part in the regenerative process, so we triggered neuro-degeneration and at the same time blocked Activin A. The difference was dramatic.

'Regeneration all but ground to a halt,' Vissel said, according to a GIMR release.

'After these initial experiments, we thought that nerve cells may directly drive regeneration by releasing Activin A. We came to realise, however, that the main action of Activin A was to block inflammation in the brain after neuro-degeneration or injury,' said Vissel.

These findings were published online in the journal Stem Cells.

Patients with primary insomnia compensate with higher brain activation

Tue, 09 Jun 2009 06:11:17 PST

( from http://www.rxpgnews.com ) According to a research abstract that will be presented on Tuesday, June 9, at SLEEP 2009, the 23rd Annual Meeting of the Associated Professional Sleep Societies, patients suffering from chronic primary insomnia (PIs) have higher levels of brain activation compared to normal sleepers during a working memory test.

Results show that PIs use increased brain activation relative to good sleepers during the working memory task, particularly in areas responsible for visual-spatial attention and coordination of cognitive processes. This activation may explain how PIs maintain performance on the task despite their sleep difficulties. PIs also were found to have decreased activation in visual and motor areas, which may suggest that PIs have higher baseline activation in these regions relative to good sleepers.

According to principal investigator Henry Orff, MS, at the University of California in San Diego, Calif., these findings show that PIs, like individuals who are acutely sleep deprived, may be able to maintain performance on different tasks if they are able to compensate with increased brain activation.

"The good news is that patients with insomnia are probably able to function well in their daily lives and likely do not show significantly impaired performance," said Orff. "That said, patients may have to work, concentrate, and attend more to tasks than people who sleep well."

The study included 12 people with primary insomnia (six females) with an average age of 39.4 years, and nine good sleepers (four females) with an average age of 35.7 years.

Performance was compared between the two groups on a working memory task. Functional MRIs (FMRI) taken during the task also were compared. Behavioral performance was measured by reaction time for correct responses, number of correct responses, and number of errors committed.

The authors state that they do not know yet whether the findings suggest potential long-term implications for cognitive functioning in the future if primary insomnia is left untreated.

ESC Congress 2009: World's biggest cardiology meeting to be held in Barcelona

Wed, 03 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The European Society of Cardiology Congress 2009, the world's biggest international meeting in Cardiology will be held in Barcelona, Spain, from 29 August to 2 September.

The meeting, which is expected to attract over 30,000 delegates, will provide opportunities for education, hearing about the latest ground breaking research and gaining deeper insights into the most recent developments and innovations in the diagnosis, treatment and prevention of Cardiovascular Disease. Delegates will include clinicians, basic scientists, epidemiologists, nurses, technicians and key opinion leaders in the field.

The latest results will be presented in the Hotline and Clinical trials sessions, with unique opportunities for delegates to have face to face interactions with the investigators. In addition, over 4,000 abstracts, featuring original research, will be show cased at the meeting.

The educational aspects of the congress include the Meet and Read with the Experts sessions and the highly acclaimed FOCUS Sessions with live transmissions and practical take home messages, not to mention reports on the latest ESC guidelines.

Prevention and risk factor identification is the special theme of this year's meeting, giving an opportunity for doctors, scientists, governments and the general public to come together to discuss ways of decreasing the burden of cardiovascular disease on society. Altogether there are 50 separate sessions on prevention in the pre arranged programme, and a special abstract session focusing on prevention research.

Additional highlights of this year's meeting include new joint sessions with sister societies, such as the European Society of Medical Oncology, looking at issues such as the cardiovascular effects of oncology drugs, a full day on Congenital Heart Disease and a new joint session with the European Commission exploring the issues around how the European Commission supports cardiovascular Research. A strong component is dedicated to basic science, including a hotline session looking at the latest development, a translational bench to bedside track and a special abstract session.

For the first time ESC 2009 will offer the opportunity for delegates to gain hands-on image and device education from clinical experts. The sessions, which are being held in purpose-built classrooms, have been organised by our industry partners, will be available free on a first come, first served basis. There will also be over 80 satellite symposia and workshops featuring the latest innovations in pharma and equipment.

All this is set against the truly inspirational city of Barcelona, with is magnificent Gaudi architecture, superb cuisine and world famous football team.

ESC 2009 promises to be a true festival of cardiology. There will be opportunities for hearing about the latest ground breaking trials, continuing education, not to forget the unrivalled opportunity for networking with colleagues from all disciplines of cardiology and finding out about practices in different countries, says Professor Fausto Pinto, Chairperson of the Congress Programme committee.

Better treatment selection and improved therapies -- key to improving prognosis in acute HF

Sat, 30 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Today, acute heart failure represents the most common reason for hospitalisation in the over-65 population. Although hospital care improves symptoms in the first 24 hours after admission in around 50% of these patients, acute heart failure events still remain associated with a more than 50% mortality and rehospitalisation rate at 6-12 months. Indeed, says Professor Marco Metra from the Cardiology Department of the University of Brescia, Italy, it is the very rapid onset of symptoms and the need for urgent therapy which characterise the condition.1,2

Treatments in acute heart failure, he adds, have not undergone any great change in recent decades, despite the demand of heart failure's increasing prevalence and huge personal and public impact. Professor Metra said that treatments are still based on loop diuretics (furosemide), peripheral vasodilators (nitrates) and inotropic agents. Even the more recently approved treatments, he added, such as levosimendan in Europe and nesiritide in the USA, have been associated with uncertain effects on outcomes in randomised trials. So hospitalisations for acute heart failure are still associated with high mortality and rehospitalisation rates, he says. The burden is tremendous because of the large number of patients involved, their poor prognosis and the costs of the treatment.

In a presentation at Heart Failure Congress 2009 Professor Metra defined two major pathways along which this burden might be reduced and treatment improved:

* Better selection of treatments. To date, he said, therapy in acute heart failure has been administered with little attention to the clinical presentation of each patient. Guidelines on heart failure issued by the European Society of Cardiology in 2008 define heart failure as a heterogeneous condition and recommend that different therapies are used on the basis of clinical presentation; for example, patients with fluid overload should undergo fluid removal through diuretics or other means, patients with high blood pressure should receive mainly vasodilators, and patients with low cardiac output should be treated with inotropic agents to improve the force of the heart muscle's contraction.3

* Improved therapies. Many new agents are currently under development, said Professor Metra, which include adenosine type 1 receptors antagonists to enhance the diuretic effects of furosemide and increase renal blood flow, new vasodilators with different mechanisms of action, and new inotropic agents.

Better treatment selection and the development of new agents give us some hope that we will finally be able to improve the symptoms and prognosis of such a large patient population as that suffering from acute heart failure, says Professor Metra. However, he also emphasised that urgent therapy is one of the key recommendations of the latest European guidelines.

UnMASCing diseases of the brain

Tue, 19 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Scientists at the Wellcome Trust Sanger Institute have discovered a set of brain proteins responsible for some of the most common and devastating brain diseases. The proteins underlie epilepsy, depression, schizophrenia, bipolar disease, mental retardation and neurodegenerative diseases including Alzheimer's and Huntington's diseases.

The reason such a remarkable number of diseases are relevant to this set of proteins is that these proteins are at the heart of how brain cells function, explains Professor Seth Grant, Director of the Genes to Cognition Programme at the Wellcome Trust Sanger Institute.

Rather than taking traditional methods for studying just one protein at a time, the researchers developed a method that finds whole sets of proteins that bind to each other and form microscopic molecular machines. They were hunting for the 'engine room' of nerve cells, which is known to be inside the connections between nerve cells called synapses.

Synapses join the billions of nerve cells together in the brain and they are the location where learning and memory and many other behaviours are controlled.

We developed a new method, which led to this discovery, says Dr Jyoti Choudhary, leader of the Proteomic Mass Spectrometry team, which collaborated with Professor Grant's team on the study, and it should be equally useful in finding the basis of many other diseases in other cells and tissues of the body.

To find this key set of proteins - called MASCs (a scientific acronym for MAGUK Associated Signaling Complexes and pronounced 'mask') - the researchers adapted a method that had previously been used in yeast cells.

The method involved making a 'molecular hook' and attaching it to one protein inside brain cells of mice. They then caught the hook and pulled it out and found it brought along another 100 proteins. The set contained dozens of disease causing proteins.

This points to the new concept that the molecular machines are defective in the diseases and that they present new ways to approach therapy, says Dr Choudhary.

Not only were there many disease proteins within the molecular machines but also proteins that control the communication between nerve cells and the mechanisms of learning and memory.

This research is an important convergence of basic and clinical science, says Professor Grant. Our findings are exciting because they suggest that the molecular machine itself is at the root of many important brain diseases. This was a blue-skies research project seeking the basic mechanisms of learning and memory and it has led us into some of the inner workings of the brain.

This is a key step toward new ways to fight mental illness.

The cardiovascular benefits of daily exercise in school children are evident even after one year

Fri, 08 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) School children as young as 11 can benefit from a daily exercise programme in reducing their levels of several known risk factors for cardiovascular disease. An ongoing study, which began four years ago in the German city of Leipzig, shows already that children assigned to daily exercise lessons reduced their overall prevalence of obesity, improved their exercise capacity, increased their levels of HDL-cholesterol, and reduced their systolic blood pressure.

It's clear that children today have different lifestyles from the past, says investigator Dr Claudia Walther from the Heart Centre of the University of Leipzig. They're less active, and it was our hypothesis that an increase in their exercise activity would result in fewer risks of cardiovascular disease later in life.

The study, whose first-year results are reported at EuroPRevent 2009, randomised 188 school children with a mean age of 11.1 years (from seven classes at three different high schools) to either an active exercise programme in their school routine, or to a conventional curriculum of just two sports lessons a week. The exercise programme comprised daily supervised exercise which included at least 15 minutes of endurance training. So it was well controlled, says Dr Walther, with the teachers making sure that the programme was followed.

The first results presented here in Stockholm already show significant benefits for those in the daily exercise groups: in just one year the proportion of overweight and obese children decreased from 13% to 9%, but increased in the control group from 11% to 13%. These were statistically significant changes. Moreover, exercise capacity (as measured by VO2max) also improved significantly in the exercise groups by 29%. Similarly, levels of HDL-cholesterol and of triglycerides, and systolic blood pressure all improved in the exercise group.

Even from these first-year results we can say that regular physical activity has a significant beneficial effect on body composition, exercise capacity and cardiovascular risk markers in children, says Dr Walther, who adds that follow-up over the next 10-20 years will give some idea of how risk modification at this young age translates into benefit later in life.

The most surprising result, she says, was the effect of daily exercise on body weight, an effect not found so marked or so soon in other studies. These are normal children, explains Dr Walther, so we didn't expect such a significant reduction in the overall prevalence of obesity or excess weight.

Such findings have also raised local interest in Germany, where the investigators hope to extend the study to other neighbouring towns, and eventually to a daily exercise programme incorporated into the basic school curriculum.

It's so easy, says Dr Walther. All it needs is a little more time allocated to exercise lessons. The teachers are there, they supervise, and they all seem enthusiastic. If we can include daily exercise in the school curriculum, I'm sure we'll see an effect.

New therapy based on magnetic stimulation shows promise for non-drug treatment for migraine

Wed, 29 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A new UCSF study examining the mechanism of a novel therapy that uses magnetic pulses to treat chronic migraine sufferers showed the treatment to be a promising alternative to medication.

The therapy is called transcranial magnetic stimulation, or TMS. Study findings were presented today (April 29, 2009) during the annual American Academy of Neurology scientific meeting in Seattle.

In a previous randomized controlled clinical study by Ohio State University Medical Center, TMS was used to treat patients who suffer from migraine with aura, a condition in which a variety of mostly visual sensations come before or accompany the pain of a migraine attack. The study showed that TMS treatment was superior to the placebo given to the control group. Patients were pain-free at follow-up intervals of 2, 24 and 48 hours.

In the new study, conducted in rats, UCSF researchers focused on understanding the mechanism of action of TMS therapy -- how the treatment interacted with the brain to produce the pain-free outcomes of patients in the previous study.

The UCSF research identified potential opportunities to enhance treatment strategies in patients. One example, the study team noted, was that factors such as time and peak intensity of stimulation may be important components in the brain's response to TMS.

The data demonstrate a biological rationale for the use of TMS to treat migraine aura, said Peter Goadsby, MD, PhD, lead investigator of the study, professor and director of the UCSF Headache Center. We found that cortical spreading depression, known as CSD and the animal correlate of migraine aura, was susceptible to TMS therapy, with the wave of neuronal excitation blocked on over 50 percent of occasions.

The study findings showed that migraine aura responds to magnetic stimulation because TMS therapy blocks the wave of neuronal excitation, which is a biological system through which neurons become stimulated to fire. TMS creates a focused magnetic pulse that passes noninvasively through the skull, inducing an electric current to disrupt the abnormal brain waves believed to be associated with migraine, including CSD. CSD in humans precedes migraine with aura.

The American Academy of Neurology estimates that over 30 million Americans suffer from migraine, a syndrome characterized by recurrent, often excruciating headaches. The National Headache Foundation estimates that migraine causes 157 million lost workdays each year due to pain and associated migraine symptoms, resulting in a $13 billion burden to American employers.

Further research is needed, the UCSF team said, but the findings give neurologists a potential new treatment option for migraine sufferers unable to tolerate medication, which can cause stomach bleeding and other painful side effects.

Poor sleep quality leads to poorer prognosis after stroke

Tue, 28 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Stroke victims tend to do worse if they also have diagnosed or undiagnosed obstructive sleep apnea prior to having the stroke, according to a study presented April 28, 2009, at the American Academy of Neurology (AAN) annual meeting in Seattle.

Latha Stead, M.D., professor and chair of the Department of Emergency Medicine at the University of Rochester Medical Center, and professor of Neurosurgery, reported the findings at AAN, along with several other stroke studies measuring the factors that lead to a poor prognosis.

We know that obstructive sleep apnea has been linked to a multitude of cardiovascular problems, yet it is concerning that the vast majority of cases remain undiagnosed, Stead said. In the context of recovering from a stroke, sleep apnea can have a serious impact, and for that reason we encourage people to become more aware of obstructive sleep apnea and to get treatment.

The prospective study included 174 patients who were diagnosed with an acute ischemic stroke in the emergency department at the Mayo Clinic between June 2007 and March 2008. (Stead was the inaugural chair of the Division of Emergency Medicine Research at Mayo before recently joining the URMC.) The stroke-sleep study was conducted in collaboration with Virend Somers, M.D., Ph.D., who is well known for his work in sleep apnea.

Researchers used a standard questionnaire to assess the risk of sleep apnea among all 174 patients, sometimes aided by the patients' sleep partners. They found that 60 percent were at high risk of sleep apnea, seven patients had a previous diagnosis of sleep apnea, and those seven patients had a higher risk of death within the first month following the stroke.

After adjusting for age and stroke severity, researchers also found that high risk of obstructive sleep apnea was a predictor of having a worse outcome. Stroke patients with diagnosed or undiagnosed sleep apnea were also more disabled at the point of discharge from the hospital. Other studies have shown similar results, Stead said, but the latest research included a larger sample size compared to earlier studies.

Strokes are the third leading cause of death and the leading cause of disability in the United States. Since sleep apnea is a breathing disorder associated with the collapse of the pharyngeal airway, it causes potentially dangerous fluctuations in blood pressure.

Researchers do not know the exact mechanisms associated with sleep apnea and poorer outcomes following a stroke. But Stead noted it is more difficult for the brain and related tissue to heal when blood is not properly oxygenated during a disrupted sleep cycle. Furthermore, patients do not respond well to stroke rehabilitation programs when they are repeatedly sleep deprived.

The next step, she said, is to begin routine screening for obstructive sleep apnea as part of the emergency department evaluation of stroke patients.

Stead and research colleagues also presented a study at AAN showing that high blood sugar, or hyperglycemia, is another predictor of early death following a stroke. While other studies have shown that diabetics face poorer outcomes after a stroke, this study focused on non-diabetics or undiagnosed diabetics who had higher-than-normal blood sugar levels in the emergency department.

The important message is that in the Emergency Department setting, it's critical to investigate all of the known risk factors that indicate a poor prognosis following a stroke, Stead said. Other known risk factors include low blood pressure and irregular heart rhythm.

Stead's research is funded by a Mayo Foundation Emergency Medicine Research Career Development Award.

Gamunex improves quality of life in patients with CIDP

Sat, 25 Apr 2009 15:23:09 PST

( from http://www.rxpgnews.com ) Talecris Biotherapeutics, Inc. announced the publication of the health-related quality of life results from the largest clinical trial ever conducted in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) in the April 14, 2009 issue of Neurology. The data demonstrate that long-term treatment with Gamunex (Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified) improves and maintains health-related quality of life in patients with CIDP.

The analysis of health-related quality-of-life endpoints showed that patients who received Gamunex experienced greater improvements in physical and mental component scores compared with placebo, as measured by the Short-Form-36 (SF-36) health survey, one of the most widely used measures of health-related quality of life. Improvements in all SF-36 domains favored Gamunex versus placebo, with physical functioning, role-physical, social functioning and mental health reaching significance.

"The data provide the rationale for administering maintenance doses of Gamunex every three weeks as a means of improving health-related quality of life and preventing relapse of symptoms," according to Ingemar Merkies, M.D., Ph.D., Department of Neurology, Erasmus Medical Center, Rotterdam and Spaarne Hospital Hoofddorp, the Netherlands. The study was funded by Talecris Biotherapeutics.

CIDP is a debilitating nerve disease that results in progressive weakness in the arms and legs, causing significant disability for many individuals. Gamunex is the first and only FDA-approved product for the treatment of CIDP.

"Until now, there has been no FDA-approved dosing regimen for an effective course of intravenous immune globulin therapy to reduce neuromuscular disability and improve quality of life in patients with CIDP," Merkies said. "Data from this trial provide an effective regimen with Gamunex to achieve improvements."

"The improvement in health-related quality of life, social participation and activity supports the use of Gamunex in patients with CIDP who have responded to it in the past. It validates the benefits of every three week infusions of Gamunex." said Dr. Peter Donofrio, professor of Neurology and Chief, Neuromuscular Section of the Department of Neurology, Vanderbilt University, Nashville, Tennessee.

Estelle Benson, executive director of the GBS/CIDP Foundation International, added "The Foundation is extremely grateful to Talecris for all they continue to do for our patient community."

Study Design Details

Results from the current study were derived from the largest-ever clinical trial of patients with CIDP, titled, "Intravenous immune globulin [10% caprylate-chromatography purified] for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomized, placebo-controlled trial." The results of the trial were published in the February 2008 issue of The Lancet Neurology. To the access the abstract, click here.

In the ICE study, 117 patients with CIDP received Gamunex or placebo every three weeks for up to 24 weeks, switching from one treatment arm to the other if they failed to measurably improve on standard disability measures. Patients who improved were eligible for a 24-week extension for a total of 48 weeks of treatment. Moreover, the quality-of-life scores of those patients receiving Gamunex every three weeks for 48 weeks approached those of healthy individuals in the U.S.

There were zero discontinuations in the study due to Gamunex maintenance therapy, and 96 percent of the Gamunex infusions were free of drug-related headache. The most common drug-related adverse reactions observed at a rate of > 5 percent were headache, fever, chills, hypertension, rash, nausea and asthenia. The most severe adverse reaction observed in patients receiving Gamunex was pulmonary embolism (PE) in one patient with a history of PE.

USC partners with French drug discovery company on computer modeling effort

Fri, 24 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A single neurotransmitter, the amino acid L-glutamate, regulates countless biological systems in animals ranging from worms and insects to human beings.

But even though scientists have known for decades that glutamate functions as a neurotransmitter, and have found that numerous diseases, including possibly schizophrenia, are linked to glutamatergic transmission malfunctions, no drugs to treat these malfunctions yet exist, despite intense efforts.

Researchers on an interdisciplinary private-academic study hope to learn enough to change this situation by using large-scale computer modeling to predict synergistic interactions within glutamate systems that might be targets for new drugs.

Two University of Southern California faculty members and the drug discovery company Rhenovia Pharma of Mulhouse, France, have been awarded a Biomedical Research Partnership (BRP) by NINDS of the NIH.

Michel Baudry, a professor in the USC department of biological sciences is the PI of the project. Theodore Berger, from the USC Vtierbi School's department of biomedical engineering is the Co-PI. They will work with Dr. Serge Bischoff, the CEO of Rhenovia Pharma.

Successful funding of this proposal is a notable achievement in the sense of the uniqueness of the structure of the research team, and in terms of the novelty of the scientific approach, says Baudry. The grant will support joint research by the three partners for four years, with the total amount of funding reaching $2.3M.

Berger says the research effort is to develop a new technology of mathematical modeling and computer simulation tools to systematically explore molecular processes underlying glutamatergic synaptic transmission, and the effects of those synaptic processes on multi-synaptic cellular dynamics, and ultimately, a small network of hippocampal neurons.

This approach will not only provide an intimate understanding of the contribution of specific molecular events to synaptic plasticity and ultimately overall systems function, but also will facilitate the design of better and safer therapeutic strategies for learning and memory impairments.

While the ultimate goal is to enable effective development of drugs, the research proposed is basic understandings, according to Baudry. The problem with glutamate in terms of pharmaceuticals is that this molecule is absolutely ubiquitous throughout the body. What is therapeutic in one area can be toxic in another. The trick is to find out a way to home in on the specific neural cells you want to affect, without disturbing the others.

One target the group will focus on is the hippocampal region, critical to learning and memory. Additionally, several neurological conditions, e.g., schizophrenia, are believed to be related to regulatory disruption of the glutamatergic system, says Berger.

The research to be conducted by the USC and French research teams is centered on a detailed model of glutamatergic synaptic transmission, called EONS, first developed by Jean-Marie Bouteiller, a Research Assistant Professor working in Dr. Berger's laboratory.

Bouteiller and Berger's research on EONS was, and still is, supported by the USC Biomedical Simulations Resource (BMSR), a Center in the Biomedical Engineering Department of the Viterbi School of Engineering, dedicated to the development of new methods for mathematically modeling physiological systems.

Thus, says Baudry, the collaboration was a natural, and represents an example of the new emphasis on translational science, realized through collaborations that extend to, and include, industry, including researchers at USC, the University Louis Pasteur in Strasbourg, not far from the Mulhouse home of Rhenovia, and engineering and scientific staff at Rhenovia Pharma itself.

Coordination and management are accomplished through weekly conference calls, e-mail, and travel to and from Mulhouse, where the group recently held its first meeting.

The following 'thinking points' define the strategy the USC-Rhenovia team will follow:

1. Pharmaceutical companies are realizing more and more that treatments for diseases of interest are not going to come in the form of a silver bullet -- a single drug that acts directly on the primary receptor and that suddenly cures everything.

2. Receptors have so many regulatory sites that it is clear that there are many, many places on the primary receptors that can be used to alter receptor function; perhaps several of these sites need to be occupied by drugs to produce the desired effect; these modulatory sites evolved for a reason.

3. An increasing number of studies are finding that agents that bind to these modulatory sites often can have little or no effect when used alone, but when used in combinations they can have large effects. These synergistic effects may represent the key to how to restore appropriate functioning of neural systems that are malfunctioning due to disease or aging. In other words, several of the regulatory sites need to be occupied simultaneously, and re-establishing normal synaptic transmission will require finding appropriate levels of activation (drug concentration) of those multiple sites simultaneously.

4. Finally, and critically: finding such synergistic effects would be very difficult if not impossible to achieve experimentally. But while computationally intensive, computer simulations could potentially create a map to guide experimenters. This will require a comprehensive model, with most of the sites for regulating both the input (presynaptic mechanisms) and the output (postsynaptic mechanisms) of key neurotransmitter systems identified correctly, lots of computing power, and expertise with the systems.

Telemonitoring changes the working practice of cardiac nurses

Wed, 08 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The 9th Annual Spring Meeting of the European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions (CCNAP), organised in cooperation with the Irish Nurses Cardiovascular Association (INCA), is being held at the Royal Dublin Society, Dublin, Ireland, on 24-25 April.

The meeting - considered by many to be the premier international event for nurses and allied health professionals - will show case the latest advances in practice, education and research. The 400 plus delegates expected to attend from 26 different countries, will have the opportunity to hear wide ranging sessions covering all aspects of cardiology, including enhancing self care in heart failure populations, managing patients with ventricular assist devices, sudden cardiac death, hypertension, angina, and adult congenital heart disease, and improving primary and secondary prevention.

The theme of this year's meeting is Addressing the Challenges in Cardiovascular Care, with sessions exploring particular challenges of cardiovascular practice in the modern era, including diabetes and metabolic syndrome, behavioural change, and adherence to treatment. Sessions geared towards the practical management of cardiovascular care in daily situations will include how to incorporate guidelines into practice, take a cardiac history, improve assessment of heart sounds and interpret echo cardiograms. One innovative aspect of this year's meeting is the opportunity for health professionals to hear patients' personal perspectives on experiencing an implantable cardioverter defibrillator (ICD) storm, and having a ventricular assist device as a bridge to transplant.

The Spring Meeting is about improving cardiovascular care, and addressing the challenges we face, such as the rapid development of knowledge and technology, and the changing roles of nurses and allied health professionals, says Professor Christi Deaton, Chair person of the ESC Council on Cardiovascular Nursing and Allied Professions (CCNAP).

Mary O'Connor, President of the Irish Nurses Cardiovascular Association, who is co-hosting this year's meeting, adds: The meeting offers an invaluable opportunity for health professionals to network and meet with international colleagues to find out about the different ways of doing things. It allows best practice to be shared and will hopefully give delegates a lot of new ideas that they can introduce into their own clinical practice.

At the meeting more than 100 abstracts will be presented in poster, moderated poster and oral sessions reporting original research and clinical projects by nurses and allied health professionals. One such abstract by Ivonne Lesman (Groningen, The Netherlands) demonstrates that heart failure patients with new onset depression are significantly more likely to be readmitted to hospital (abstract 90082). The study, says Lesman, demonstrates the importance of screening for depressive symptoms in heart failure patients.

We hope that the presentation of high-quality research will encourage more nurses and allied professionals not only to read and review research, but also to conduct more well-designed studies that build evidence for practice, says Professor Deaton.

Mayo study shows simple finger device may help predict future heart events, such as heart attack

Thu, 26 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla. - Results of a Mayo Clinic study show that a simple, noninvasive finger sensor test is highly predictive of a major cardiac event, such as a heart attack or stroke, for people who are considered at low or moderate risk, according to researchers.

The study will be presented Tuesday, March 31, 2009 at 11:30 a.m. EDT at the American College of Cardiology Annual Scientific Session in Orlando (0917-7).

The noninvasive finger test device, called the EndoPAT by Itamar Medical, measures the health of endothelial cells by measuring blood flow. Endothelial cells line the blood vessels and regulate normal blood flow. Research has shown that if the cells don't function properly - a condition called endothelial dysfunction - it can set the stage for atherosclerosis (hardening of the arteries) and lead to major cardiovascular health problems. Previously, there was no simple test for endothelium function, says Amir Lerman, M.D., a cardiologist at Mayo Clinic and the senior author of the study.

Forty-nine percent of patients whose EndoPAT test indicated poor endothelial function had a cardiac event during the seven-year study. Researchers at Mayo Clinic and Tufts-New England Medical Center in Boston used the device to test 270 patients between the ages of 42 and 66 and followed their progress from August 1999 to August 2007. These patients already knew that they had low-to-medium risk of experiencing a major heart event, based on their Framingham Risk Score. The score is the commonly used risk predictor and was developed from the Framingham Heart Study, a longitudinal study of heart disease.

Some of their risk factors included high blood pressure, high cholesterol, obesity and a family history of heart disease, Dr. Lerman says. The results of the study may help identify a discriminating tool beyond the Framingham Risk Score, he says. And the results of these individual tests may help physicians change a patient's medications or recommend other therapies, so they don't have a heart attack or stroke later on.

The test may be used in an individualized medicine model of risk assessment of the patients, Dr. Lerman says.

EndoPAT, which received U.S. Food and Drug Administration approval in 2003, consists of digital recording equipment and two finger probes that look like large thimbles. For the test, which takes 15 minutes, probes are placed on each index finger and hooked up to a small machine to measure blood flow. A standard blood pressure cuff is placed on one arm; the arm without the cuff is the control. A reading of the fingers' blood flow rate begins, and then the blood pressure cuff on one arm is inflated for a few minutes and then deflated, allowing for three timed readings.

The role of the inflated blood pressure cuff is to occlude and then release blood flow to assess reactive hyperemia (RH), the normal blood flow response that occurs when occlusion is released. In the study, 49 percent of the patients who went on to have a cardiac event had a low RH score.

A low RH signal - indicating a lower blood flow response - is consistent with endothelial dysfunction and potentially impaired vascular health that may lead to or serve as a marker for future events, Dr. Lerman says.

Brain surgery on Monday, home on Tuesday

Wed, 25 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) MAYWOOD, Ill. -- Norma Wooley checked into Loyola University Hospital on a recent Monday morning for brain surgery to repair a life-threatening aneurysm.

She went home on Tuesday, cured of the slurred speech, drooping face and worst headache of her life.

Dr. John Whapham used a less-invasive technique that's becoming increasingly common in brain surgery. The Loyola University Health System neurologist inserted a catheter (thin tube) in an artery in Wooley's leg and guided it up to her brain. The catheter released tiny platinum coils into the bulging aneurysm, effectively sealing it off.

She went home the next morning with a Band Aid on her leg, Whapham said.

Whapham, 36, is part of a new generation of neurologists who are using catheters to repair aneurysms, open clogged arteries, extract blood clots and repair blood vessel malformations in the brain. He also opens blocked carotid arteries in the neck. The catheter technique is much less invasive and risky than traditional brain surgery, which involves cutting a large opening in the skull.

Catheter technology, originally developed for heart surgery, has been modified for narrower and more challenging blood vessels in the brain. There has been a huge evolution in devices over the last five years, Whapham said. Whapham is an assistant professor in the Departments of Neurology and Neurological Surgery, Loyola University Chicago Stritch School of Medicine.

Whapham recently joined Loyola University Health System. He is board certified in neurology and has completed fellowships in endovascular neurosurgery, diagnostic cerebral angiography and stroke/neuro-critical care.

Wooley, 54, of St. Charles, Ill., is one of Whapham's first patients at Loyola. Her successful treatment illustrates the benefits of performing brain surgery with catheters rather than scalpels.

Wooley had a cerebral aneurysm, a weak spot in a blood vessel that balloons out and fills with blood. About six million Americans -- 1 in 50 people -- have brain aneurysms that could rupture. Each year, aneurysms burst in about 25,000 people, and most die or suffer permanent disabilities, according to the Brain Aneurysm Foundation.

Wooley's aneurysm was roughly one-fourth inch across, and shaped like a gumball. It could burst at any time and cause a debilitating or fatal stroke. Her clinical presentation was suspicious for what's called a sentinel hemorrhage, in which an aneurysm on the brink of rupture will often perforate without catastrophic clinical or radiographic findings. One day at work, Wooley began slurring her words, as if she had been drinking. Her mouth and eyelid drooped, and she had a headache that felt like someone was hitting her on the back of her head with a baseball bat. An ambulance took her to a local hospital, and she was transferred to Loyola.

My brain was ready to explode, she said.

Traditional open-brain surgery to repair aneurysms is highly invasive, and recovery can take months. Many patients wind up with cognitive deficits that can, for example, make it impossible to do complex jobs.

Between 80 percent and 90 percent of brain aneurysms can be repaired with less-invasive catheters. Tiny coils of platinum wire are passed through the catheter and released into the bulging aneurysm. The aneurysm fills up with coils, causing the blood to clot. It's like filling a bathtub with concrete, Whapham said.

A landmark clinical trial known as ISAT randomly assigned aneurysm patients to receive either open brain surgery or catheter surgery. The catheter group had significantly lower rates of death and disability. Whapham said catheter surgery techniques and devices have improved dramatically since the study was published in 2002 in the British journal

Stroke survivors improve balance with tai chi

Mon, 23 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Stroke can impair balance, heightening the risk of a debilitating fall. But a University of Illinois at Chicago researcher has found that stroke survivors can improve their balance by practicing the Chinese martial art of tai chi.

Christina Hui-Chan, professor and head of physical therapy at UIC, has studied and used tai chi as a way to improve balance and minimize falls among healthy elderly subjects. Now she and a colleague have seen similar results in a group of stroke survivors.

The study used 136 subjects in Hong Kong who had suffered a stroke more than six months earlier. Participants were randomly assigned to a tai chi group or a control group that practiced breathing, stretching and other exercises that involved sitting, walking, memorizing and reasoning.

Tai chi consists of constant coordinated movement of the head, trunk and limbs requiring tremendous concentration and balance control. Participants learned a simplified form that had been shown to be beneficial to arthritis patients.

Patients were trained in small groups by physical therapists in a weekly class, then practiced at home three days a week for one hour. They received 12 weeks of training but were able to learn the technique in as little as eight. The goal was to make the patients as independent in their treatment as possible, Hui-Chan said.

They were then tested for their ability to maintain balance while shifting weight, leaning in different directions, and standing on moving surfaces to simulate a crowded bus. In these tests the tai chi group out-performed the control exercise group. The two groups performed about the same on another test, which was not focused solely on balance but involved sitting, standing, walking, and returning to sit down.

The tai chi group did particularly better in conditions that required them to use their balance control, Hui-Chan said. In only six weeks, we saw significant improvements. The ability to shift your weight is very important because all reaching tasks require it.

While learning tai chi is not easy, Hui-Chan has found that most people can learn the art if taught by a trained instructor. Many Chinese practice tai chi in morning group exercises, and Hui-Chan thinks the experience can work for Americans and other western nationalities.

It can be taught at community centers, YWCAs or YMCAs, or in parks in the summer, she said.

Hui-Chan said that benefits of tai chi include improved strength and cardio fitness. Group classes also provide a healthy social gathering for isolated seniors at a fraction the cost of physiotherapy or personal training.

Cardiac imaging highlighted at Biennial ICNC-9

Mon, 16 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ICNC9, the key international scientific meeting on Nuclear Cardiology and Cardiac CT, is taking place in Barcelona, 10-13 May.

ICNC, a joint venture between the ESC Working Group on Nuclear Cardiology and Cardiac Computed Tomography, the European Association of Nuclear Medicine (EANM) and the American Society of Nuclear Cardiology (ASNC), now in its 18th year, aims to promote excellence in Nuclear Cardiology and Cardiac CT through practice, education and research. The biannual meeting - which gathers over one thousand cardiologists, nuclear medicine doctors, radiologists, imaging technologists, nurses, physicists, and industry representatives from over 40 countries - provides a unique opportunity for delegates to learn more about the state of the art of cardiac imaging, and its future directions.

Imaging represents a real growth area in cardiology, with more and more guidelines now stating the need for imaging. But it's still not currently the main stream, making it imperative that more cardiologists get up to speed in the area, says Professor Juhani Knuuti, Co-Chair of the meeting.

Cardiac imagining is the key for decision-making in cardiology, permitting resources, such as medications and coronary revascularization, i.e. cardiac surgery or angioplasty, to be used for maximum patient benefit, says Professor Robert Hendel meeting Co-Chair.

ICNC9 is a really important medical meeting because everything novel in the field of imaging will be highlighted here, says Professor Jeroen Bax, former chair and programme chair of ICNC. Such sub-speciality meetings, which are tightly focussed on specific areas of cardiology, offer a really valuable opportunity to advance frontiers in medicine. At ICNC9, all cardiac imaging modalities will be featured including nuclear cardiology techniques (such as SPECT and PET), cardiac computed tomography (CT), cardiac MR, and echocardiography. This year, a special focus will be present on cardiac CT, with sessions being held in every available time slot at the meeting.

Revolutionary advances in cardiac imaging and its applications will be featured during this meeting. Additionally, ICNC9 provides a great opportunity for health care professionals to meet and develop new strategies for imaging within clinical practice says Professor Hendel.

At the 2009 meeting, there will be a particular focus on integrating the different imaging technologies for the ultimate benefit of patients. When treating patients, clinicians shouldn't apply modality based thinking, but should be using the technology best suited to the clinical questions they want to answer, says Professor Knuuti.

An example of the way imaging technologies can be helpfully combined is using CT for information on the anatomy of coronary arteries and nuclear tests for information on haemodynamics. Combining these two modalities provides both the best diagnostic and prognostic information, with a much more complete picture for the patient, says Professor Bax.

A unique feature of ICNC is that the programme can be accessed at different levels of expertise. Essential sessions review fundamentals to help new comers to the field get up to speed, Core Curriculum sessions address the current big clinical questions, and Advance sessions consider the future directions. Technological advances to be covered will include:

Young black adults have higher rates of stroke than white counterparts

Mon, 16 Mar 2009 01:22:07 PST

( from http://www.rxpgnews.com ) In Florida, black young adults are hospitalized for stroke at a rate three times higher than their white and Hispanic peers, a new study by University of South Florida researchers reports. The study was presented today at the American Heart Association's Council on Epidemiology and Prevention Annual Conference and appears in the online version of the international journal Neuroepidemiology.

Disparities in stroke outcomes between black and white patients have been widely reported for years. While overall death rates for stroke are down, blacks bear a disproportionate burden of disease, disability and death from strokes, said lead author Elizabeth Barnett Pathak, PhD, associate professor of epidemiology at the USF College of Public Health.

"Our study shows this black-white disparity hasn't improved. In fact, it's clear that the gap emerges even at relatively young ages – among adults hospitalized for strokes in their 20s and 30s – and widens with increasing age," Dr. Pathak said. "It points toward an urgent need for primary prevention of hypertension, obesity, and other stroke risk factors among African Americans to eliminate disparities in stroke."

While most strokes occur among the elderly, stroke in young adults can lead to chronic illness and disability that places a terrible burden on the victims and their families, said Michael Sloan, MD, professor of neurology and director of the USF Stroke Program at Tampa General Hospital. "If the stroke is severe it can be very debilitating, impacting the ability of young people to work and raise their families."

And even in young adults strokes can be fatal. The Florida study found 8 to 10 percent of stroke patients died before discharge from the hospital.

The USF researchers examined more than 16,000 stroke cases of young adults hospitalized for stroke in Florida from 2001 through 2006. The study included men and women, ages 25 to 49, from the three largest ethnic groups in Florida: whites, blacks and Hispanics. Among the findings:

The age-adjusted stroke hospitalization rate for blacks was three times higher than for whites or Hispanics. Stroke hospitalization rates for Hispanics were similar to those for whites.

The rates at which hospitalized stroke patients died were 15 percent higher for blacks than whites, but this disparity was explained by a greater prevalence of stroke risk factors and complicating illnesses such as diabetes, coronary artery disease and heart failure.

In contrast, Hispanic stroke patients were 27 percent less likely to die in the hospital than whites after taking risk factors and other illnesses into account. More studies are needed to determine whether Hispanic ethnicity actually confers any sort of protective advantage, the researchers said.

Black stroke patients were more likely than whites and Hispanics to have been diagnosed with high blood pressure, morbid obesity or drug abuse. White stroke patients were more likely to have been diagnosed with high cholesterol, alcohol abuse or cigarette smoking.

The majority of black stroke patients (56 percent) where women, while the majority of Hispanic and white patients were men.

Hispanics were more likely than blacks and whites to suffer a hemorrhagic stroke, triggered by the rupture of a blood vessel in the brain. As with the elderly, the most common type of stroke in younger adults, known as ischemic stroke, was caused by the obstruction of blood flow to the brain.

While the USF study did not find an increase (or decrease) in young adults hospitalized for stroke in Florida, Dr. Sloan is concerned that tough economic times may lead to rise in strokes and other cardiovascular incidents. "When people stop taking their blood pressure pills and other medications because they can no longer afford it, they have strokes and heart attacks," he said.

Preventing a second stroke is focus of study at Rush University Medical Center

Tue, 03 Mar 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Rush University Medical Center is participating in a National Institutes of Health (NIH) study to determine the best course of treatment to reduce the risk of stroke patients suffering another stroke. The study will determine if aggressive treatment of stroke victims for high blood pressure and cholesterol, along with placing a stent to widen a narrowed artery in a patient's brain, is better than intensive medical therapy alone.

The study is called the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracrainal Stenosis or SAMMPRIS. The study is the first to look at the long-term benefits of the Wingspan stent, the only FDA approved stent designed to open clogged arteries in the brain.

Prior to the Wingspan stent, the options for treating stroke patients were limited. Blood-thinning medications are commonly used to treat narrowing of intracranial arteries, but studies have found that stroke patients who had severe artery blockages of 70 percent or more have a 22 percent chance of having another stroke within the first year, said Dr. Shyam Prabhakaran, section head of Cerebrovascular Disease and Neurological Critical Care at Rush

Dr. Demetrius Lopes, neuroendovascular surgeon at Rush, was the first physician in Illinois to use the Wingspan stent. The catheterization procedure involves carefully threading a hair-like filament from a tiny incision on the inside of the thigh through the body's arteries and veins up to the patient's brain. After reaching the site of the blockage, the plaque-filled brain vessel is first opened using a microscopic balloon that is inflated, pressing aside the blockage. The stent is placed to hold the plaque against the artery wall and keep the blood flowing through the brain.

Rush has the largest experience with the Wingspan stent in Chicago. The stent has been quite effective in preventing recurrent strokes in more than 100 cases, said Lopes.

A preliminary study released last year that was funded by the NIH found that the Wingspan stent was successfully deployed in nearly all cases and significantly reduced arterial blockages in the short term. But data on the long-term benefit of the stent, compared to medical treatment alone, were inconclusive, prompting the launch of the SAMMPRIS trial.

A randomized trial such as SAMMPRIS is one of the most powerful scientific tools to bring us definitive answers, said Lopes. The results from this trial will improve the management of patients at risk for stroke.

In addition, the study will determine the effectiveness of intensive medical management of underlying conditions such as high cholesterol and high blood pressure. There has not been a landmark study looking at how the aggressive treatment of these underlying conditions can benefit stroke victims.

This is a seminal study, one funded by the NIH and having significant implications on future management of patients with narrowed arteries in the brain, said Prabhakaran. It will determine whether we should be offering stenting as a primary treatment of narrowed arteries or whether medications are sufficient.

The five-year SAMMPRIS study plans to enroll 764 patients from approximately 60 sites in the Unites States. Intensive medical therapy for all participants will consist of aspirin, clopidogrel (a blood thinner), and aggressive risk factor management primarily targeting blood pressure and cholesterol. Approximately half of the patients in the trial, selected randomly, will have a stent placed. Study participants will be evaluated by a neurologist every four months and will meet with internists who will manage the vascular risk factors.

To be eligible for this trial, patients must be between the ages of 30 and 80 years, have had a stroke or TIA within 30 days, and have stenosis (narrowing) of a major intracranial artery (blood vessel in the brain).

Thrombolysis therapy of benefit 9 hours post-stroke

Mon, 09 Feb 2009 12:01:21 PST

( from http://www.rxpgnews.com ) Some patients who suffer a stroke as a result of a blockage in an artery in the brain may benefit from a clot-busting drug nine or more hours after the onset of symptoms. The findings are published in the online edition of Radiology.

"Stroke is the third leading cause of death in the U.S.," said the study's lead author, William A. Copen, M.D., Director of Advanced Magnetic Resonance Neuroimaging at Massachusetts General Hospital (MGH) in Boston. "Every hour that we can add to the treatment window would allow vastly more stroke patients to be treated with potentially life-saving therapy."

The most common type of stroke is called ischemic stroke. These strokes occur when a blood clot blocks a blood vessel supplying blood to the brain. Some ischemic strokes can be treated with thrombolytic, or clot-busting, therapy using tissue plasminogen activator (t-PA), which helps dissolve the blockage. However, the window of opportunity to safely administer the medication is generally considered to be just three hours. Because few patients get to the hospital to be diagnosed and treated within that time frame, fewer than seven percent of patients receive the drug.

In this retrospective study, researchers analyzed the test results of 109 ischemic stroke patients at MGH. The testing methods included two different MRI scanning techniques: perfusion MRI, which measures blood flow in the brain, and diffusion MRI, which measures the movement of water molecules in tissue.

"Comparing the lesions that we see in these two MR images reveals which areas of the brain are threatened by a lack of blood flow, but could still be salvageable," Dr. Copen said. "A mismatch between the lesions suggests that a patient might still benefit from thrombolytic therapy."

In the study, most patients with blockage in a proximal artery, close to the base of the brain, continued to demonstrate a diffusion-perfusion mismatch between nine and 24 hours after the onset of their strokes.

"Patients who have a mismatch have been successfully treated up to nine hours after stroke onset, which is already much longer than the guidelines allow, Dr. Copen said. "Our findings suggest a need for a clinical trial to measure the effectiveness of thrombolytic therapy more than nine hours after the onset of an ischemic stroke."

Enriched environment as a child helps reverse memory problem

Tue, 03 Feb 2009 22:52:27 PST

( from http://www.rxpgnews.com ) A new study by researchers from Rush University Medical Center and Tufts University School of Medicine using mice indicate that a child's memory and the severity of learning disorders may be affected by what his or her mother did when she was a child.

Findings from the study are published in the February 4th issue of The Journal of Neuroscience.

Neuroscience researchers studied the brain function of pre-adolescent mice that have a genetically-created defect in memory. When these young mice were given an enriched environment, which is exposure to stimulatory objects, enhanced social interaction and voluntary exercise for two weeks, the memory defect, caused by inhibiting the formation of Ras-GRF1 and Ras-GRF2 proteins, was reversed.

After a few months, the same mice were fertilized and they gave birth to offspring that had the same genetic mutation. However, the offspring had no indications of the memory defect even though the offspring were never exposed to an enriched environment like their mothers.

Previous research in mouse models has shown that early exposure to an enriched environment while pregnant can also positively affect offspring.

"What is so unique about this study is that we provided an enriched environment during pre-adolescence, months before the mice became pregnant, yet the beneficial effect reached into the next generation," said Dean Hartley, PhD, neuroscience researcher at Rush University Medical Center and study co-investigator. "The offspring had improved memory even without an enriched environment."

"We were able to demonstrate that environmental enrichment during youth has dramatic additional powers," said Hartley. "It can enhance the memory in future offspring of enriched juvenile mice."

To prove that that improved memory of the offspring was not the result of better nurturing by mothers who were enriched when they were young, a number of offspring were raised by non-enriched foster mothers. Even in the offspring raised by non-enriched mothers, they still maintained an improved memory.

"This example of 'inheritance of acquired characters' was first proposed by Jean- Baptiste Lamarck in the early 1800s. However, it is incompatible with classical Mendelian genetics, which states that we inherit qualities from our parents through specific DNA sequences they inherited from their parents. We now refer to this type of inheritance as epigenetics, which involves environmentally-induced changes in the structure of DNA and the chromosomes in which DNA resides that are passed on to offspring," said Larry Feig, PhD, professor of biochemistry at Tufts University School of Medicine.

Previous research has shown that a relatively brief exposure to an enriched environment in both normal and memory-deficient mice unlocks an otherwise latent biochemical control mechanism that enhances a cellular process in nerve cells called long-term potentiation (LTP). LTP is thought to be involved in learning and memory. This enhancement was detected in pre-adolescent mice but not in adult mice, reflecting the brain's higher plasticity in the young.

"This is the first study to demonstrate an inheritance of a change in a signaling pathway that promotes LTP and enhancement of memory formation, and that defects caused by a genetic mutation can be reversed by what the mother is exposed to during her youth," said Hartley.

The phenomenon described in this study indicates that juvenile enrichment affects LTP in the next generation. However, the study found that it does not in subsequent generations because the effect of the enriched environment wears off faster in the offspring.

A mesh-like network of arteries helps wih blood flow to the brain after a stroke

Fri, 30 Jan 2009 14:29:39 PST

( from http://www.rxpgnews.com ) A grid of small arteries at the surface of the brain redirects flow and widens at critical points to restore blood supply to tissue starved of nutrients and oxygen following a stroke, a study published this week has found.

Surface arteries brain dive into the brain to feed capillaries. The mesh-like network adjusts to restore normal supply when blood slows after a stroke.

“This is optimistic news,” said David Kleinfeld, a physics professor at the University of California, San Diego, whose group studies blood flow in animal models of stroke.

Damage from stroke can continue for hours or even days as compromised brain tissue surrounding the core injury succumbs to deprivation of oxygen and nutrients.

“This is the area doctors are trying to protect after a stroke,” said Andy Shih, a postdoctoral fellow in Kleinfeld’s group who conducted the experiments. “Those neurons are teetering on the edge of death and survival.”

Previous work with animal models had found that blood flow can persistently slow in the aftermath of a stroke, which would hinder the delivery of drugs that might help recovery. But those studies only measured the speed of the blood.

By measuring both the speed of blood cells moving through individual small arteries and the diameters of the same vessels, the scientists found that the arteries dilate to maintain a constant delivery of blood cells.

“You find that the velocity has gone down, but that the diameter—on average—exactly compensates,” Kleinfeld said.

Patrick Drew and Philbert Tsai in Kleinfeld’s group, and Beth Friedman and Patrick Lyden, MD, of the neuroscience department at UC San Diego’s School of Medicine co-authored the paper. Lyden, whose contributions to a 1995 study proved that the drug tPA can reverse the course of stroke when administered promptly, also directs the UC San Diego Stroke Center. The Journal of Cerebral Blood Flow and Metabolism published their new finding online January 28.

Key to this resilience, it seems, is the structure of the vascular network overlying the brain.

“Vessels on the surface of the brain have a mesh-like architecture,” Kleinfeld said. “One consequence of that is that it operates like a grid system that redistributes “current flow as you need it.”

“City traffic freezes a lot less than you would think because once a street gets bogged down, you can move over to another street,” he said. “This seems to be what happens on the surface of the brain.”

Flows through the surface vessels reversed and stalled, as previously observed, but those changes helped to redistribute blood to ensure a steady supply though vessels that penetrate into the brain.

Shih focused his measurements on small arteries, called arterioles, at the point where they dive into the brain to supply a discrete patch of the cortex, a juncture that is vulnerable to occlusions that can cause microstrokes this group’s previous work has found.

“These are extremely important. A single penetrating arteriole will feed a column of tissue,” Shih said. “These are bottlenecks in flow.”

The penetrating vessels neither reversed nor stalled, even though many connected to loops and bridges in the vascular network that could have allowed that to happen. Even when the pressure dropped permanently as a result of stroke damage, wider lanes allowed the network to deliver red blood cells at the same rate.

“Diameter is the major determinant to how blood actually flows through vessels. Open up a blood vessel a little bit and you’ll have a huge change in the amount of blood that goes through,” Shih said. “Blood flow comes back, and it seems that these vessels are very resistant to the stroke. They function quite normally.”

Facial Movement important in speech perception

Sun, 25 Jan 2009 01:40:12 PST

( from http://www.rxpgnews.com ) The movement of facial skin and muscles around the mouth plays an important role not only in the way the sounds of speech are made, but also in the way they are heard according to a study by scientists at Haskins Laboratories, a Yale-affiliated research laboratory.

"How your own face is moving makes a difference in how you 'hear' what you hear," said first author Takayuki Ito, a senior scientist at Haskins.

When, Ito and his colleagues used a robotic device to stretch the facial skin of "listeners" in a way that would normally accompany speech production they found it affected the way the subjects heard the speech sounds.

The subjects listened to words one at a time that were taken from a computer-produced continuum between the words "head" and "had." When the robot stretched the listener's facial skin upward, words sounded more like "head." With downward stretch, words sounded more like "had." A backward stretch had no perceptual effect.

And, timing of the skin stretch was critical — perceptual changes were only observed when the stretch was similar to what occurs during speech production.

These effects of facial skin stretch indicate the involvement of the somatosensory system in the neural processing of speech sounds. This finding contributes in an important way to our understanding of the relationship between speech perception and production. It shows that there is a broad, non-auditory basis for "hearing" and that speech perception has important neural links to the mechanisms of speech production.

Details of this study are reported in an article titled "Somatosensory function in speech perception" by Ito, Mark Tiede, and David J. Ostry which appeared in the Proceedings of the National Academy of Sciences (PNAS). All of these researchers are scientists affiliated with Haskins Laboratories. Tiede is also at the Research Laboratory of Electronics at the Massachusetts Institute of Technology and Ostry is a Professor in the Department of Psychology at McGill University.

Haskins Laboratories was founded in 1935 by the late Dr. Caryl P. Haskins. This independent research institute has been in New Haven, Connecticut since 1970 when it formalized affiliations with Yale University and the University of Connecticut. The Laboratories' primary research focus is on the science of the spoken and written word.

Blocking LRP1 can reduce toxic effects of clot-busting drug tPA

Sat, 24 Jan 2009 16:35:06 PST

( from http://www.rxpgnews.com ) Since the introduction of the life-saving clot-busting drug tPA more than a decade ago, evidence has been accumulating that tPA (tissue-type plasminogen activator) can be a double-edged sword for a brain affected by stroke. Although it remains the only FDA-approved treatment for acute stroke, tPA can also contribute to inflammation and brain cell damage.

Scientists at Emory University School of Medicine are testing strategies for blocking LRP1, a molecule that appears to transmit inflammation signals triggered by tPA. They have found that in mice, genetically removing LRP1 from certain brain cells called microglia softens tPA's impact on the brain.

The results, published online this week by the American Journal of Pathology, suggest that blocking tPA's toxic effects could make it safer and allow doctors to use it more often on patients experiencing a stroke.

"tPA is a protein released naturally by the body in response to a blood clot," says Manuel Yepes, MD, PhD, assistant professor of neurology at Emory University School of Medicine. "But it's clearly not just lysing the clot."

Doctors in community hospitals can often be reluctant to administer tPA to patients who appear to be having a stroke, Yepes says. One reason is that tPA has been shown to increase the risk of bleeding in the brain, he says.

Researchers have shown that tPA treatment increases the permeability of the blood-brain barrier, and that it can cross from the blood vessels into the brain tissue, generating inflammation. tPA targets cells called microglia, which are similar to white blood cells of the immune system, although they live in the brain.

"Our strategy was to show that by blocking LRP1, you can prevent the inflammatory response to tPA," Yepes says. "This can be done either genetically, by deleting LRP1, or perhaps pharmacologically."

Yepes and his colleagues are now testing a natural inhibitor of LRP1 called RAP in the laboratory. Co-treating or even pre-treating stroke patients with RAP might soften tPA's effects.

Researchers had previously been unable to examine the effects of deleting LRP1, a protein involved in transporting cholesterol and other molecules around the brain, because mice completely lacking the gene die in the womb.

Yepes and his colleagues collaborated with Dudley Strickland, PhD, professor of surgery and physiology at University of Maryland School of Medicine, who provided mice deficient in LRP1 in macrophages (white blood cells) and microglia only.

The authors showed that the genetically altered mice have half the number of activated microglia in the brain after treatment with tPA. In addition, the volume of brain tissue damaged by a simulated stroke was cut in half in the genetically altered mice.

Study to look into early diagnosis of Alzheimers disease by MRI

Sat, 17 Jan 2009 05:13:12 PST

( from http://www.rxpgnews.com ) Researchers at UC Davis have launched an innovative study to determine whether closer examination of magnetic resonance imaging (MRI) scans can detect the onset of Alzheimer's disease even before patients begin to show the symptoms of cognitive decline that are the hallmarks of the condition.

The study also will look at whether MRI scan analysis can be used to predict the likely rate at which Alzheimer's disease patients' brains will deteriorate, and how quickly they will lose their ability to think and reason.

"We want to 'squeeze more juice' out of MRIs that are used to detect the presence of Alzheimer's disease," said Owen Carmichael, an assistant professor in the Department of Neurology and an adjunct professor in the Department of Computer Science. "We also want to predict the likely rate of decline."

Alzheimer's is a progressive and fatal brain disease affecting as many as 5 million Americans. It destroys brain cells, causing problems with cognition — memory, logical reasoning and other mental skills. It is the most common form of dementia, and there is no cure.

There also is no definitive way of determining whether or not a person has Alzheimer's disease in its early stages. Currently, physicians ask patients to perform a series of cognitive tests to diagnose the condition. But some loss of memory is normal in healthy aging individuals, so it can be difficult early on to determine whether or not a person has Alzheimer's.
MRI imaging is used to detect atrophy of a portion of the brain called the hippocampus, which is vital to learning and memory. But some atrophy — or shrinkage — of the hippocampus occurs in normal aging. Carmichael, who is the principal investigator for the study, hopes to use MRI to detect the distinct pattern of shrinkage across the hippocampus that occurs in the brains of Alzheimer's patients.

"Alzheimer's disease tends to make the hippocampus atrophy in a specific pattern — it spreads from one hippocampus region to another, killing cells as it goes. We can quantify not only the overall size of the hippocampus, but also localized patterns of damage. That's what I mean by 'squeezing more juice' out of the MRIs," he said.

Carmichael and his colleagues will test a new, computational method of measuring atrophy in various sub-regions of the hippocampus to see whether Alzheimer's produces distinct spatial patterns of hippocampal atrophy that would distinguish it from patterns of mild cognitive impairment found in normal aging.

"We hope that using this technique we can provide a method for differentiating people who will experience healthy cognitive aging from those who will experience cognitive decline due to diseases like Alzheimer's. For those who will experience cognitive decline, we hope to predict its rate of progression," Carmichael said.

The researchers will test the efficacy of the new computational MRI imaging method, called Localized Components and Analysis (LoCA), developed by Carmichael and colleagues Nina Amenta, an associate professor in the Department of Computer Science, and computer science graduate student Dan Alcantara.

The researchers will use LoCA to analyze MRI scans of 800 adults who are part of a large, publicly available database called the Alzheimer's Disease Neuroimaging Initiative (ADNI). The database contains more than 4,000 MRI scans of the brains of patients diagnosed with Alzheimer's, adults with mild cognitive impairment, and those without symptoms. They will examine whether the spatial patterns of hippocampal atrophy differ among the three groups.

They also will analyze in more detail the MRI brain scans of adults who underwent expensive, experimental imaging tests that try to detect aspects of Alzheimer's pathology in the brain to determine whether LoCA can tell the difference between those who appear to have the pathology and those that do not. They will use the results of these comparisons to analyze additional MRI scans from the ADNI database, to see whether the method can predict rates of cognitive decline in Alzheimer's.

"Once diagnosed, patients, physicians and families have no reliable method for anticipating how fast cognitive functioning will decline," Carmichael said. "We hope that this method will change that."

Social stigma to dementia percieved greater in UK

Thu, 15 Jan 2009 14:40:08 PST

( from http://www.rxpgnews.com ) A new study has found that in spite of their universal health care system which facilitates access to free dementia care, older adults in the United Kingdom are less willing to undergo dementia screening than their counterparts in the U.S. because the Britons perceive greater societal stigma from diagnosis of the disease than do Americans.

Researchers surveyed 125 older adults in Indianapolis and 120 older adults in Kent, England, on their opinions on the perceived harms and benefits of dementia screening. None of those surveyed had been diagnosed with dementia, however significantly more of the U.K. participants (48 percent) had close friends or relatives who have or had Alzheimer's disease compared to U.S. participants (27 percent).

The study of public attitudes toward early detection of dementia across different health-care systems was conducted by researchers from Indiana University in the United States and the universities of Kent and London in the United Kingdom. The research was funded in part by the U.S. National Institute on Aging, and appears in an advance online publication of the International Journal of Geriatric Psychiatry.

"From my prospective, it was a genuine surprise that having a universal health care system, which provides services and support to all those who need it, didn't protect from perceived stigma and negativity," said the study's corresponding author, Malaz Boustani, M.D., assistant professor of medicine at the IU School of Medicine and a Regenstrief Institute research scientist.

Even when taking into account education and race differences, Britons indicated greater concern with the stigma of diagnosis, with potential loss of independence, and with emotional suffering than their American counterparts.

"This study, which investigates the acceptance and societal stigma associated with dementia – something very difficult to track – provides us with a unique insight as Americans debate the pros and cons of universal health care," said study first author, Michael Justiss, Ph.D., assistant professor of occupational therapy, School of Health and Rehabilitation Sciences, Indiana University-Purdue University Indianapolis.

Dementia is a growing global public health problem in both countries leading to a high burden of suffering for society with an annual cost of $100 billion in the U.S. and $10 billion in the U.K.

"In spite of the fact that new strategies for both treatment and prevention of dementia are currently being developed, this study gives us an initial awareness so that we can develop improved care pathways for dementia. We hope the United Kingdom's Dementia Strategy published in the next few months will consider some of this study's findings," said Chris Fox, MB, BS of the University of Kent, who led the British researchers.

"This pilot study is the beginning, not the end. We need to do further exploration with a bigger sample, with different types of individuals. But this study which found deep concern about dementia screening despite access to health care services in U.K., clearly tells us that there are many issues we must explore as we attempt to retool the American health care system. We have to be careful not to put the horse before the cart as we debate national health care in the U.S.," said Dr. Boustani, who is also an IU Center for Aging Research center scientist. Dr. Boustani has written extensively on the dementia screening.

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Standardized test battery to aid those with Down syndrome

Mon, 12 Jan 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Researchers at The University of Arizona are developing a set of standardized tests that could improve the lives of people with Down syndrome.

The condition, which occurs once in every approximately 800 to 1,000 live births, is signaled by the presence of an extra 21st chromosome. Those with Down syndrome often have mild to severe developmental disabilities, and other health issues that include heart defects and the early onset of Alzheimer's dementia. New research also suggests connections between chromosome 21 and other genes point to some of these problems.

For the past 25 years, Lynn Nadel has been studying the cognitive aspects of Down syndrome. Nadel, a Regents' Professor in the UA psychology department, has spent the bulk of his career studying the hippocampus, the area located deep within the brain that is associated with memory and spatial navigation.

Nadel said while some researchers may be involved with Down syndrome, he was drawn to it as an interesting scientific problem. The hippocampus develops later than other parts of the brain, including after birth, and is susceptible to disruptions. Nadel became interested in the possible implications of environmental impacts such as fetal alcohol syndrome, autism, lead and mercury poisoning and others.

A lot of things that happen early in life have an impact on the development of this structure because it is still plastic and developing, Nadel said.

Since the hippocampus is one of the later developing parts of the nervous system, it made sense to think there might be some connection between this late development story and cognitive problems in Down syndrome.

Starting in the mid-1980s, Nadel began to speculate on the possibility that problems with hippocampal development might also contribute to cognitive problems in Down syndrome. He said the existing literature and later research added to the mounting evidence connecting the two. His own neuropsychological work and cognitive testing supported the case.

In the early 1990s, Nadel and his colleagues in Denver decided that in order to make any further progress, they would need a very accurate profile of the cognitive deficits in children with Down syndrome. For a while, their research slowed until Roger Reeves, a heart specialist at Johns Hopkins who had worked on heart problems in Down syndrome, asked about Nadel's research.

Like the hippocampus, there are anatomical features in the heart that develop very late, like the closing of the valves. Reeves wondered if children with Down syndrome were more likely to have late-developing heart problems. On one of his heart projects, Reeves related the probability of heart defects not just to chromosome 21, but other genes that interact with the extra chromosome 21, and had shown the feasability of using that as a predictor.

Nadel thought he could do that for cognitive function, and suggested they team up to determine the best way to profile cognitive deficits to use in combination with genetic and intervention studies. This could be a way to determine what else contributes to the exact outcome to any particular child with Down syndrome.

Nadel and Reeves brought in genetics experts from Emory University to complete the team.

We're also planning to bring in researchers in Pittsburgh and setting up two or three sites around the country to increase the sample size to get even more exact data on how to make a direct link between the genetic profile of a given child with Down syndrome and their cognitive outcome. You want to predict as early as possible their likely trajectory, and which kids you should intervene with more aggressively, Nadel said.

Most researchers assume that the range of variability in children with Down syndrome is no different than for the rest of the population. There is a very large range in typically developing children, everything from high-functioning to low-functioning. And there is every reason to assume the same in Down syndrome.

We're trying to figure out how to most accurately assess as early as possible, within the first year or two of life. What is the likely trajectory. The kids at age 1 you could already predict by looking at their genetic makeup and a few cognitive tests that we're trying to work out that would be sensitive to cognitive function in the first year or two of life.

An accurate assessment of a child's learning trajectory would enable parents and medical and education specialists time to develop appropriate strategies for learning and possible drug therapies.

The earlier we can make the prediction, the better advice we can give to parents about what they need to do to optimize their kids' development, Nadel said.

The key to finding out where people with Down syndrome are cognitively, he said, is through the use of standardized tests.

We're working on developing a standardized battery for 8 to 18 year olds, the adolescent range that is easiest to develop tests that have adequate controls for in the developing population. Once we have that figured out for that age range, we want to move in both directions.

That includes tests for much younger children, but also for those in the 25-35 age range. Until a few decades ago, many with Down syndrome died in their 30s and 40s, usually from heart problems. Medical advances have helped stave off heart-related deaths, but it exposed another health risk for this group.

By age 35, and certainly by age 40, just about everyone with Down syndrome has characteristic neuropathology associated with Alzheimer's, Nadel said. Every individual with Down syndrome who has died past that age all have this pathology.

What we also know is that for individuals with Down syndrome who are alive past age 35, about 35 to 40 percent actually seem to have early Alzheimer's. They all have mental retardation, either high or low functioning, but they don't seem to have dementia of the Alzheimer's type. This itself presents another interesting scientific question. Why do they have what appears to be the pathology associated with Alzheimer's disease, but don't have it? Given that they all have the neuropathology, we need another indicator, like behavior testing, to find out which ones have dementia or are more likely to get it.

Developing tests requires a large number of subjects. Several dozen have been tested in Tucson, Baltimore and Atlanta. Nadel is creating a fixed battery of nine or 10 tests that can be useful worldwide.

The test battery has to be precise in its ability to tell researchers about a particular brain structure. Three of these tests are targeted as assays, like blood tests that detect the presence of blood sugar. Performance on a cognitive test indicates how well the subject's hippocampus or the prefrontal cortex, another structure thought to be compromised in Down syndrome, are functioning.

The battery has to be designed to be quite specific to only assay one particular structure and not be affected by the function of other structures, Nadel said.

They have to be targeted and precise. They also have to be fairly short. All kids have a short attention span, so we want tests that are precise and targeted and short. They typically are computer based, but not always.

They also are portable. We want to be able to test not only on kids or individuals who can make it into a university or hospital laboratory, but in schools and homes, he said.

Nadel said a number of criteria constrain the development of this battery but the goal is to have something that is repeatable, to test subjects initially and then bring it back a month later and still get reliable results.

Down syndrome also cuts across languages and cultures, so tests have to work the same way anywhere in the world.

Luckily, we're based in Tucson, where there is a substantial Hispanic population. A number of students working on the project speak both English and Spanish fluently, so they were able to help us navigate testing kids who come from Spanish-speaking families. So we've been able to jump that hurdle, Nadel said.

Nadel and his group are now establishing contacts with colleagues in Barcelona, Spain. One of his students is going to do her study-abroad semester in Argentina and will look into what is happening there. The family of another student runs a home for kids with developmental disabilities in Indonesia.

There are cultural differences in how people with developmental disabilities are treated. But worldwide Down is emerging from the closet and kids are being mainstreamed and treated as educable and worth doing something for. That's happened over the last 20 or so years as a function of what we're learning about it.

Nadel said the test battery is near completion, likely in 2009, after a year and a half in development and presentations at meetings. A journal article is near as well.

We're pretty much there, and should have a finished product that we will be happy to share with others doing the same thing around the world who want to use this standardized approach. People are pretty much waiting on us to finish.

Standardized tests, he said, will also aid other researchers working on drug treatments and other kinds of early stimulation, especially for clinical trials that require before-and-after comparisons.

Nadel also has found popular support from the parents of children with Down syndrome. The research testing was developed so that the children would enjoy it. There are boring parts, but Nadel said they try to work around those.

The parents in Tucson and Denver and wherever I've worked with these groups are enormously positive and cooperative about the work. Most of our research is from private foundations that get their money from families with kids with Down syndrome and want to see this research go forward.

What it will make possible is a way of assessing kids, but also for assessing the efficacy of clinical trials. That's been missing. There's always been lots of anecdotal stories about the value of ginkgo or vitamin E. What has been lacking in the field has been some sort of solid scientific way of assessing the virtues of and value of things. So, parents are very excited that we're getting close to having this kind of measurement tool.

The research has also drawn interest from UA students. Nadel said this avenue of research is an area where the rewards are obvious.

One of the most exciting things is how many students want to work on this project. Six or seven right now. It's been an immediate hit. This is good and interesting science and connects to the real world and they can sink their teeth into it and make a difference. It's been a magnet for undergraduate students who want to get involved in research, in something connected to the world.

This one of those perfect examples of how teaching and research mesh completely. In the classroom you talk about brain development and cognition and how it goes right and how it goes wrong. Here is the opportunity for undergrads to actually go in and discover something about that process and make a difference.

Smokers with family history of brain aneursyms at high risk of stroke

Thu, 01 Jan 2009 12:26:14 PST

( from http://www.rxpgnews.com ) A new study shows that people who are smokers and have a family history of brain aneurysm appear to be significantly more likely to suffer a stroke from a brain aneurysm themselves. The research is published in the December 31, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology and will appear in the January 6, 2009, print issue of Neurology.

Subarachnoid hemorrhage, a type of bleed from a brain aneurysm which leads to a stroke, is deadly in about 35 to 40 percent of people.

In the study, scientists looked at 339 people who suffered a stroke from a brain aneurysm and 1,016 people who had not had a stroke due to an aneurysm. Current smokers made up half of the group that had a stroke. The other half had never smoked or had smoked in the past.

The research found people who smoked and had a family history of stroke were more than six times more likely to suffer a stroke than those who did not smoke and did not have a family history of stroke or brain aneurysm. The study also found that people with a family history of stroke could cut their risk by more than half by quitting smoking. The results were the same regardless of high blood pressure, diabetes, alcohol use, body mass index and education level.

"While all people should be advised to quit smoking, our findings suggest that there is an interaction so that if you smoke and you have a family history of aneurysms, you are at an extremely high risk of suffering a stroke from a ruptured brain aneurysm," says study author Daniel Woo, MD, with the University of Cincinnati in Ohio and member of the American Academy of Neurology.

UT faculty members win American Heart Association awards for advancing research

Tue, 23 Dec 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Faculty members at The University of Texas Health Science Center at Houston (UTHSC-Houston) were honored for their work in the fight against heart disease at the 2008 American Heart Association's Scientific Sessions in New Orleans. Heart disease is the nation's No. 1 killer.

UT faculty members recognized were: Nobel Laureate Ferid Murad, M.D., Ph.D., director emeritus of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the UTHSC-Houston; John Holcomb, M.D., director of the Center for Translational Injury Research at the UTHSC-Houston; and Raffaella Lombardi, M.D., Ph.D., IMM postdoctoral fellow. The AHA scientific sessions were Nov. 8 -12.

Murad was named one of 13 Distinguished Scientists for 2008 by the American Heart Association. The prestigious award was created to honor researchers whose work has advanced the understanding of cardiovascular disease and stroke.

Murad found that nitroglycerin and several related heart drugs induce the formation of nitric oxide and that this gas acts to increase the diameter of blood vessels in the body, according to the American Heart Association. He shared the 1998 Nobel Prize in Physiology or Medicine with Robert Furchgott and Louis Ignarro for their major discoveries involving nitric oxide as a unique signaling molecule in the cardiovascular system.

Nitric oxide is one of the most important signaling molecules produced within our body. Dr. Murad's contributions to the field have revolutionized the concept of cell signaling by a gaseous molecule. Potential applications are far-reaching across multiple organ systems. Discovery of this pathway has allowed new therapeutic strategies to control blood pressure, correct conditions of endothelial dysfunction and even treat erectile dysfunction, said Nathan Bryan, Ph.D., assistant professor of molecular medicine at the IMM.

Murad completed his undergraduate work at DePauw University and received his M.D. and Ph.D. from Case Western Reserve University. He completed a medical residency at Massachusetts General Hospital and a fellowship at NIH in the Heart Institute.

Holcomb received the 2008 Lifetime Achievement Award in Trauma Resuscitation Science, which was established in 2003 to recognize leaders in this field. Holcomb's contributions to trauma medicine include increased hemorrhage control through dressings, tourniquets and intravenous methods, as well as trauma informatics and systems.

Each year the American Heart Association selects one surgeon to receive a Lifetime Achievement award for their contributions to the resuscitation of critically ill or injured patients. Dr. Holcomb, while serving in the U.S. Army (now retired) made significant contributions to the understanding and treatment of injured patients in war zones as well as civilian trauma. His contributions have led to a new paradigm in transfusion of patients sustaining blood loss. He well deserves this recognition, said Richard Andrassy, M.D., professor and chairman, the Denton A. Cooley, M.D., Chair in Surgery and the Jack H. Mayfield, M.D. Distinguished University Chair at The University of Texas Medical School at Houston.

Holcomb is past commander of the United States Army Institute of Surgical Research at the Brooke Army Medical Center in San Antonio. He finished his undergraduate work at Centenary College and received his degree of medicine at the University of Arkansas Medical School in Little Rock. He completed an internship and residency in general surgery at the William Beaumont Army Medical Center in El Paso.

Lombardi won the 2008 Louis N. and Arnold M. Katz Basic Science Research Award Prize for Young Investigators, which is given to the best scientific presentation at the annual scientific sessions of the American Heart Association.

Lombardi presented a manuscript describing the origin of the fat cells in the heart in a disease condition referred to as arrhythmogenic right ventricular cardiomyopathy, which is an important cause of sudden cardiac death in the young, especially athletes. In this disease, which is a genetic disorder, excessive fat cells replace cardiac myocytes in the heart, particularly the right side of the heart. She and her colleagues showed that fat cells originate from the stem cells in the heart that through a unique mechanism convert to fat cells in the presence of genetic mutations.

The Katz Award is the most prestigious award given to young investigators in basic cardiovascular research by the American Heart Association, said Ali Marian, M.D., professor and director of the Center for Cardiovascular Genetic Research at the IMM. The work (of Lombardi) could lead to the development of new therapies aimed at preventing the cardiac stem cells from switching a muscle fate to a fat cell fate and therefore, prevention of this potentially deadly disease.

Lombardi received her medical degree and clinical training in internal medicine and cardiology at Federico II University of Naples, Italy. She joined Marian's research group in the IMM three years ago and earned a doctorate in clinical physiopathology and experimental medicine from Federico II University of Naples during this period.

University of Miami biomedical engineer

Wed, 17 Dec 2008 04:59:37 PST

( from http://www.rxpgnews.com ) CORAL GABLES, FL (December 17, 2008)-Baruch Barry Lieber, Ph.D., professor of biomedical engineering at the University of Miami College of Engineering and professor of radiology at the University of Miami Miller School of Medicine, has received a grant from the National Institute of Neurological Disorders and Stroke (NINDS), to support research studies that offer promise in the treatment of brain aneurysms.

The $1.9 million grant administered over a period of five years will help fund the development and optimization of assistive technology for a device created by Lieber to help heal brain aneurysms.

Dr. Lieber's project addresses the important need for methods to treat brain aneurysms, said Eugene Golanov, M.D., Ph.D., program director of NINDS. Although there are clinically available techniques to prevent aneurysm rupture, they are not ideal for all patients. We are optimistic that Dr. Lieber's work will lead to a useful alternative therapy.

The project for which Lieber won the award is titled, Flow Divertors to Cure Cerebral Aneurysms. The focus of the research is to develop a tubular mesh-like device, which can be placed into cerebral arteries via catheters, to reduce the blood flow in an aneurysm, while keeping the arteries open to supply oxygen to the brain tissue.

Slowing down the blood flow within the aneurysm leads to natural clotting, which prevents rupture of the aneurysm and elicits a healthy scar-response from the body, thus restoring the diseased arterial segment to its normal state, explained Lieber.

Dr. Lieber, is a professor of biomedical engineering in UM's College of Engineering, with a secondary appointment in the Department of Radiology at the Miller School of Medicine. He works in conjunction with the Vascular Biology Institute (VBI) on the medical campus. The VBI deals with all aspects of vascular function in health and disease with a focus on angiogenesis, coronary artery disease, aneurysm, and stroke, explained Keith Webster, Ph.D., director, professor and Walter G. Ross chair of the VBI.

Dr. Lieber spearheads the aneurysm and stroke studies and has developed technology that is changing the field and will directly impact clinical treatments, said Webster. We are working with Dr. Lieber's group within the VBI combining our novel gene and stem cell technologies with his cutting edge bioengineering approaches to develop new treatments that can be rapidly translated into clinical applications.

The collaboration between the College of Engineering and the Miller School of Medicine is part of an ongoing effort to forge interdisciplinary cooperation, said Ozcan Ozdamar, PhD., professor and chairman of the University of Miami Department of Biomedical Engineering.

Dr. Lieber is an outstanding biomedical engineer and researcher with an established record, said Ozdamar. His award is the result of our continuing collaboration between the College of Engineering and the Miller School of Medicine, aimed at finding innovative solutions to challenging medical problems

Delay in school start time helps pupils sleep better and decreases crash rates on the road

Mon, 15 Dec 2008 02:10:38 PST

( from http://www.rxpgnews.com ) A study in the Dec. 15 issue of the Journal of Clinical Sleep Medicine shows that after a one-hour delay of school start times, teens increased their average nightly hours of sleep and decreased their "catch-up sleep" on the weekends, and they were involved in fewer auto accidents.

When school started one hour later students averaged from 12 minutes (grade nine) to 30 minutes (grade 12) more self-reported nightly sleep. The percentage of students who got at least eight hours of sleep per weeknight increased significantly from 35.7 percent to 50 percent; students who got at least nine hours of sleep also increased from 6.3 percent to 10.8 percent. The average amount of additional weekend sleep, or "catch-up sleep," decreased from 1.9 hours to 1.1 hours. Daytime sleepiness decreased, as reported by students using the Epworth Sleepiness Scale. Average crash rates for teen drivers in the study county in the two years after the change in school start time dropped 16.5 percent compared to the two years prior to the change, while teen crash rates for the rest of the state increased 7.8 percent over the same time period.

"It is surprising that high schools continue to set their start times early, which impairs learning, attendance and driving safety of the students," said senior author Barbara Phillips, MD, director of the UK Healthcare Good Samaritan Sleep Center in Lexington, Ky.

A survey concerning the sleep habits of students from an entire county-wide school district in Kansas was distributed before and after a change in school start times. In April 1998, (Year One), a total of 9,966 students (66 percent of the total population of middle and high-school students enrolled in the county) from grades six to 12 completed questionnaires concerning their sleep habits on school nights and non-school nights and various aspects of daytime functioning. In April 1999, (Year Two), 10,656 students (72.8 percent of the total population of middle and high-school students enrolled in the county) filled out the same questionnaire. School times during Year One were 7:30 a.m. for high schools and 8 a.m. for middle schools. In Year Two high schools and middle schools started one hour later at 8:30 a.m. and 9 a.m.

Separate crash rates were computed for the county that changed high school start times and for the state as a whole. State-collected measures of collision statistics by age and residence of driver were used to compute crash rates per 1,000 licensed drivers for teen drivers before and after the change in school start times in both the county in which the start times changed and in the rest of the state where start times remained unchanged.

The county crash rates were considerably higher than the rest of the state prior to the change in school start times. According to the authors the elevated crash rates may have been caused by the fact that the study county was in the center of a rapidly expanding metropolitan area. Phillips attributed the decrease in auto accidents after the change in school start times to improved vigilance, as the students were able to get more sleep.

The authors report that both social and biological pressures appear to cause a shift in sleep patterns during the transition to adolescence, with the result that adolescents stay up progressively later. As a result, adolescents get an inadequate amount of sleep due to early school start times, which increases their daytime sleepiness and may in turn increase their odds of crashing their vehicles while driving.

Studies focusing on early diagnosis and treatment of epilepsy with minimal side-effects

Sun, 07 Dec 2008 14:20:05 PST

( from http://www.rxpgnews.com ) Early diagnosis and treatment that quickly achieves seizure freedom with nominal side effects is the key goal to epilepsy management. Three studies highlighted at the AES annual meeting address this goal from different vantage points:
The course to seizure freedom? Identifying factors that may change the landscape of epilepsy treatment to improve patients' quality of life.
New EEG technology that may facilitate accurate seizure screening by non-specialists in urgent care settings.
Task force report on disparity in standards for Epilepsy Monitoring Units amidst rise in number of epilepsy treatment centers.

"Each clue we uncover in understanding epilepsy and how to suppress the disruptions it causes for those affected takes us closer to the goal of successfully treating this chronic condition. Data from this year's meeting lead us towards answers about characteristics we can focus on to more effectively diagnose and treat epilepsy," said Dennis D. Spencer, M.D., AES President, Harvey and Kate Cushing Professor and Chair of Neurosurgery, Yale University School of Medicine. "This is especially critical because we know that an estimated one-third of seizures are not controlled with existing therapies."

Epilepsy Patients Achieving Seizure Freedom More Quickly, According to New Analysis

An analysis of epilepsy patients demonstrated that the time to seizure freedom significantly decreased by 10% every year from 1995 to 2005, according to data presented by Jukka Peltola, MD, PhD, Department of Neurology, Tampere University Hospital, Tampere, Finland.

Dr. Peltola and his colleagues studied records of 571 epilepsy patients aged nine to 78 years, who were diagnosed and treated in Tampere University Hospital from 1995 to 2005. Using various methods of analysis, they identified the amount of time for 70% of patients to achieve seizure freedom:

Patients diagnosed in 1995-1998: 10 years.
Patients diagnosed in 1999-2001: 6 to 7 years.
Patients diagnosed in 2002-2005: 4 years.

"The first-line treatment protocol has not changed over the duration of this study in Finland, but several other changes in the landscape may have contributed to this positive trend. These include new second- and third-line agents, earlier and more aggressive intervention, and greater access to advanced MRI and EEG technology," explained Dr. Peltola. "We are actively analyzing this data further to ascertain the reasons for the decrease in time to seizure freedom. If identified, this could make an important clinical difference."

New EEG Technology—a Seizure Vector Algorithm—Facilitates Seizure Screening in Urgent Care Settings

A group of researchers from Infinite Biomedical Technologies (IBT) and The Johns Hopkins University School of Medicine presented findings demonstrating the accuracy of investigational screening technology designed to assess if a patient's symptoms should be classified as a seizure or another condition.

"Access to an EEG reading, the gold standard for identifying and classifying seizures, is limited in most urgent care settings. Often the EEG machine and/or technologists are not readily available to the Emergency Department (ED), and eventual diagnosis by a specialist may be delayed for hours, or in some cases days," said study author Peter W. Kaplan, MB, FRCP, Professor of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD.

To address this problem, the collaborative team, with grant support from the National Institutes of Health, designed the Seizure Vector (SV) algorithm to express EEG readings as a numeric seizure score. Based on the score, ED staff could quickly classify and triage patients. Potential classifications include:

Epileptic seizures: refer to a neurologist for further evaluation.
Non-epileptic events: refer for neurological, medical or psychiatric evaluation.

The team's hope is that this technology, when used in the ED setting, will enable first-response personnel to screen for seizures in patients and make rapid triage decisions, such as timely referral to a specialist for evaluation, diagnosis and treatment.

To validate the algorithm, researchers collected EEGs from 40 adults with a variety of seizure types, and a blinded epileptologist classified them into "normal" or "seizure" categories. A total of 2,035 episodes of seizures and 3,867 episodes of normal data were recorded. When the SV algorithm was applied to the same recordings, it differentiated between "seizure" and "normal" episodes with 95.0% sensitivity and 95.2% specificity.

Surveys Reveal Lack of Consensus on Patient Care, Safety Measures in Epilepsy Monitoring Units

A new AES survey of physicians and nurses provided the basis for a working group discussion at this week's meeting regarding a need for the creation of standards in patient care and safety measures in epilepsy monitoring units (EMUs) across the United States.

Patients are admitted to EMUs to determine if they are having seizures, to consider if surgery is an option, for medication changes, or other diagnostic procedures. Some of the monitoring procedures require sleep deprivation and/or taking patients off medications to provoke seizures for simultaneous recording of symptoms and related brain wave activity.

The surveys evaluated EMU practices related to these monitoring procedures, as well as patient supervision. Results revealed discrepancies across EMUs in these areas, with relatively few physicians and nurses reporting that their facilities had protocols in place for seizure monitoring or patient supervision.

"In the continuum of patient care, EMUs are critically important and can significantly drive outcomes," said EMU Study Group member Gregory L. Barkley, MD, Clinical Vice Chair, Department of Neurology, Henry Ford Hospital. "This is why the AES has made it a priority to examine EMUs and formulate best practices and guidelines that will establish a standard, increase efficiency and, most importantly, improve patient outcomes."

Mayo Clinic finds it generally safe to withdraw anti-seizure medication in children with epilepsy

Sun, 07 Dec 2008 04:59:37 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. - A new Mayo Clinic study found that it is generally safe to withdraw anti-seizure medications in children with epilepsy who have achieved seizure-freedom while on the medication. Researchers found that these children were not at high risk of subsequently developing intractable epilepsy. The study will be presented on Sunday, Dec. 7, at the American Epilepsy Society's annual meeting in Seattle.

Epilepsy is a disorder characterized by the occurrence of two or more seizures. It affects more than 3 million Americans. Approximately 10 percent of affected children have intractable epilepsy, a condition in which medications alone do not control seizures and seizures have a disabling effect on quality of life.

It is often recommended that children with epilepsy who become seizure-free on anti-seizure medications be withdrawn from the drugs to avoid side effects of long-term use. Those potential side effects include cognitive slowing, incoordination, weight change, behavioral decline, and liver damage, says Katherine Nickels, M.D., a Mayo Clinic pediatric neurologist and an author of this study. However, few previous studies had examined the risk of intractable epilepsy following withdrawal of anti-seizure medication, and the reported risks varied widely.

Dr. Nickels and a team of Mayo Clinic researchers set out to determine the frequency of intractable epilepsy in children who withdrew from anti-seizure medication after a period of seizure-freedom. The team reviewed the records of 241 children, ages 1 month to 16 years, who were diagnosed with new-onset epilepsy between 1990 and 2000. They identified 152 children who were diagnosed and treated with anti-seizure medication and had at least five years of follow-up. Of those, 56 children (37 percent) achieved seizure-freedom and were withdrawn from the medication. After an average follow-up of eight years, 20 children (36 percent) experienced at least one seizure recurrence. Fifteen of these children re-started the anti-seizure medication, and eight (53 percent) achieved seizure-freedom within one year, two (13 percent) achieved seizure-freedom after two years and only three (20 percent) developed intractable epilepsy. Overall, only 5 percent of the 56 children who withdrew from anti-seizure medication following seizure-freedom developed intractable epilepsy.

The risk of children developing intractable epilepsy after withdrawal of anti-seizure medication was only 5 percent, which is similar to the risk of intractable epilepsy at the time of initial diagnosis of epilepsy in children, says Dr. Nickels. Therefore, the children who achieve seizure-freedom on anti-seizure medication should be considered for withdrawal without high risk of intractable epilepsy.

Sudden Unexpected Death In Epilepsy

Mon, 17 Nov 2008 12:10:58 PST

( from http://www.rxpgnews.com ) A new study by researchers at UC Davis Medical Center suggests that the sudden unexplained deaths of some epilepsy patients may be a result of their brains not telling their bodies to breathe during seizures.

"Significant drops in blood oxygen levels are more common than we thought in patients with partial seizures," said study senior author Masud Seyal, a professor of neurology at UC Davis Medical Center and director of the UC Davis Comprehensive Epilepsy Program.

The study, published online in the Oct. 24 issue of the journal Brain, studied Sudden Unexpected Death in Epilepsy, what doctors call SUDEP for short, to examine deaths of epileptics not explained by repeated convulsive seizures, accidents or other mishaps.

"What we've known for a long time is that SUDEP appears to be the most important cause of increased mortality in epilepsy patients. What we haven't known is what causes it," Seyal said.

The findings suggest that some cases of SUDEP may result from the brain not signaling the patient to continue breathing during seizures, though more conclusive evidence is needed, he said.

"It may have to do with an abnormal heart rhythm or it just may be that the brain stops sending the proper signals to maintain normal breathing," Seyal said.

In the retrospective study, Seyal and his colleagues examined records of 300 seizures in 57 epilepsy patients with chronic, recurrent, unprovoked seizures. They compared patients with severe convulsive seizures to those with milder symptoms like transient confusion, lip smacking and head turning.

One-third of all seizures were associated with drops in blood-oxygen levels below 90 percent. Seyal said he was surprised to find that 12 percent of these patients' blood oxygen levels actually dropped below 70 percent during their seizures.

They also discovered that seizures in the temporal lobe of the brain are more often associated with significant drops in blood-oxygen levels and that males are more likely than females to experience dangerously low levels of oxygen during seizures.

The findings support the idea that some cases of SUDEP may be caused by a lack of brain signaling that makes the patient keep breathing, though scientists need to do more research before they know for sure, Seyal said.

The study is important, Seyal said, because it suggests that hospitals that monitor inpatients for seizures should use both continuous blood-oxygen monitoring that sets off alarms when blood levels are too low and around-the-clock monitoring by staff or relatives.

In a hospital setting, blood-oxygen levels below 85 percent require intervention, such as giving supplemental oxygen, turning the patient on his side or suctioning the patient's airway, to help the patient breathe.

Patients hospitalized for seizure monitoring in the UC Davis Comprehensive Epilepsy Program must have a relative or friend with them around the clock who can recognize their seizures and summon assistance when they occur, in addition to constant blood-oxygen monitoring.

Some medical centers also use video monitors that are continuously monitored by hospital staff. But many do not employ this kind of close monitoring.

"Our data show that it's important that respiratory parameters be closely monitored in the hospital," Seyal said.

The best strategy to reduce the likelihood of SUDEP is to promptly and effectively control patients' seizures, Seyal said.

Most seizures can be stopped with medication. Patients with seizures poorly controlled with medication often are candidates for surgery, which can have a high success rate. To perform the surgery, however, patients must be observed in the hospital, their medication must be reduced and seizures allowed to take place.

"This is the only way we can pinpoint the region of the brain responsible for the seizures and know where to operate," he said.

Seyal and his colleagues are working to determine the best ways to deal with patients who have severe drops in oxygen levels with seizures.

"The important thing here is to see how we can intervene to deal with the hypoxemia when it happens," he said.

Dr. Henry Barnett becomes first person outside Europe to receive Karolinska Stroke Award

Wed, 29 Oct 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Dr. Henry JM Barnett, London, Ontario, receives the Karolinska Stroke Award for Excellence in Stroke Research. The prize amounts to 100,000 SEK. The laureate will receive the prize from the President of Karolinska Institutet Harriet Wallberg-Henriksson during the Karolinska Stroke Update meeting in Stockholm November 17, 2008. Barnett is the first non-European to receive this prestigious award. The Karolinska Institutet also awards the Nobel Prize annually.

Barnett's key research field is prevention of stroke. For younger colleagues, he will be primarily remembered as an enthusiastic coordinator of the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Together with a European study of similar design this trial provided the scientific evidence for operation on tight atherosclerotic manifestations on the carotid artery of the neck, since then one of the most important interventions to prevent recurrent stroke after transient or mild cerebrovascular warning symptoms.

Before the NASCET study, Barnett was leading another extensive trial, with quite a different outcome. In North America, and some other medical centres in the world, clinics were established to perform extracranial-intracranial (EC-IC) bypass surgery, in patients with total occlusion of one of the major supplies to the brain, the internal carotid artery. Through an opening of the skull bone, arteries on the outside of the skull were connected with those on the surface of the brain. The EC-IC bypass study showed that these operations did not benefit patients and in the mid 1980s, these operations were almost totally stopped. Today we know that before any conclusions can be made on the severity of an occluded carotid artery, an evaluation of alternative (collateral) blood flow supply to the brain is essential.

Even earlier, in 1970, Barnett was leading the Canadian Aspirin Trial which established, for the first time, that any antiplatelet drug could prevent diseases (in this case stroke) due to arterial thrombosis.

Barnett was born in Newcastle upon Tyne in England and moved with his parents to Canada as a child. He entered medicine at the University of Toronto where he graduated in 1944. He did his junior rotating internship at the Toronto General Hospital and later completed training in neurology in Toronto in 1950. After two years at Queen Square in London, UK, and later a research assistant in Oxford, he obtained a fellowship from the Royal College of Physicians and Surgeons of Canada (F.R.C.P.(C.)). From 1952 to 1967 he was neurologist at the Toronto General Hospital and from 1966 to 1969 Chief of the Division of Neurology at Sunnybrook Medical Centre. In 1969 he was invited to become the Chief of the Division of Neurology at The University of Western Ontario and Victoria Hospital in London, Ontario. From 1974 to 1984 he served as Chairman of the Department of Clinical Neurological Sciences at The University of Western Ontario. In 1986, he co-founded the Robarts Research Institute and was named its first Scientific Director.

Barnett's extraordinary contributions to stroke research have changed the management of millions of stroke patients. The implementation of his research has prevented an unaccountable number of strokes. He has shown the strength of research by revealing that some routinely used procedures were supported by science, others were not.

For these contributions, Dr. Henry JM Barnett is awarded the Karolinska Stroke Award for Excellence in Stroke Research in 2008.

Scientist plans to test for blood pressure genes affected by age

Wed, 24 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) A geneticist at The University of Texas Health Science Center at Houston plans to scan the genomes of about 4,000 people in the hopes of finding out why blood pressure often increases as young adults age.

The two-year study by principal investigator Myriam Fornage, Ph.D., is funded with a new $1.1 million grant from the Genes, Environment and Health Initiative (GEI) of the National Institutes of Health. The grant was one of six announced today during the second round of funding from the program aimed at finding genetic factors that influence common disorders.

High blood pressure is the single most important predisposing factor to cardiovascular disease, said C. Thomas Caskey, M.D, director/chief executive officer of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the UT Health Science Center. This research could lead to the identification of genes through which environmental factors such as aging act to accelerate disease. Knowledge of these genes opens new opportunities for therapeutic targets.

The GEI researchers receiving grants will use genome-wide association studies. In such studies, researchers rapidly scan markers across the complete sets of DNA, or genomes, of large groups of people to find genetic variants associated with a particular disease, condition or trait.

According to Peter Doris, Ph.D., an IMM professor, Age is clearly the most important environmental risk factor for high blood pressure. What is novel and potentially powerful about Dr. Fornage's project is the focus on age and blood pressure interaction.

Fornage said little is known about the genetic cause of high blood pressure and that her study is among the first to look at blood pressure genes in the context of age. We're trying to determine how genes influence the gradual rise in blood pressure experienced by many people as they move from being a young adult to a middle-aged person, she said.

The study will begin by examining the genomes of about 4,000 people who were recruited into a research project in the mid-1980s and who have had their blood pressure checked periodically. The project is called the Coronary Artery Risk Development in Young Adults (CARDIA) Study and participants were between 18 and 30 when it began.

To confirm the findings, scientists from the Human Genetics Center at The University of Texas School of Public Health will attempt to replicate the results with participants in: the Bogalusa (La.) Heart Study; the Atherosclerosis Risk in Communities Study (ARIC); and the Rochester (Minn.) Family Heart Study.

D. Michael Hallman, Ph.D., an assistant professor at the UT School of Public Health, will coordinate tests with the Bogalusa (La.) Heart Study. Alanna Morrison, Ph.D., an associate professor at the UT School of Public Health, will coordinate tests with the Rochester (Minn.) Family Heart Study.

Our ultimate goal is to discover pathways that could be targeted for therapeutic intervention, Fornage said.

Thrombolysis in stroke- upto 4 and 1/2 hours

Mon, 15 Sep 2008 12:33:52 PST

( from http://www.rxpgnews.com ) The time span in which treatment should be given for acute ischaemic stroke – i.e. stroke caused by a clot or other obstruction to the blood supply – can be lengthened. This according to a study from the Swedish medical university Karolinska Institutet, the results of which can bring about more effective and safer treatments for stroke sufferers.

In the event of acute ischemic stroke, treatment with 'clot-busting' drugs – thrombolysis – should be administered as early as possible. Failure to do so might leave the treatment doing harm than good since it increases the danger of haemorrhage. Prevailing praxis is for thrombolysis to be given only to patients who reach hospital within three hours after the onset of stroke.

However, an international study led by Professor Nils Wahlgren at Karolinska Institutet now shows that it is safe to administer the treatment up to four and a half hours after the stroke.

The researchers compared 11,865 patients treated within three hours of stroke with 644 patients who, for various reasons, were treated within three to four and a half hours afterwards. The results show that the risk of haemorrhage complications and death was not significantly higher for the later treatment. Nor was there any difference between the two groups in the percentage of patients displaying impaired functionality in everyday activities three months after stroke.

"The data we are now publishing will make it possible for many more patients to receive thrombolysis," says Professor Wahlgren. "This is important, because it'll not only alleviate their suffering, but also help to reduce the costs of stroke for society."

Possible changes to the European guidelines for the treatment of stroke will be under discussion at Karolinska Stroke Update, a conference due to be held in Stockholm on 16-18 November. Here, consideration will also be taken of the results of another, as yet unpublished, randomised study co-led by Professor Wahlgren.

UIC leads multi-center study to evaluate blood flow and stroke risk

Tue, 09 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) The University of Illinois at Chicago has been awarded a five-year, $2.1 million grant from the National Institute of Neurological Disorders and Stroke to lead a multi-center study to assess blood flow and stroke risk.

Ischemic strokes -- the type caused by clots rather than bleeds in the brain -- account for 80 percent of all strokes and represent a major source of death and disability. They are often caused by atherosclerosis, a build-up of plaque inside the walls of blood vessels.

Advances in endovascular techniques, such as threading a catheter to open up a blockage, or placing a stent in a vessel, provide new treatment options for patients with stroke. But these interventions carry risks, and physicians don't always know which patients are appropriate candidates for these procedures.

There's been a lot of emphasis in prior medical research on the type of stroke that affects the anterior circulation, or blood supply to the major lobes in the front of the brain, says Dr. Sepideh Amin-Hanjani, UIC assistant professor of neurological surgery and principal investigator of the study.

But there's another set of arteries that supply the back part of the brain, including the brainstem, which is a smaller, but in some ways, a much more functionally important part of the brain with a lot of important real estate, she said.

Even a very small stroke in this area of the brain can have very devastating consequences, Amin-Hanjani said.

Until recently, it has been difficult for researchers to measure blood flow in the vertebral arteries to the back of the brain. But they hypothesize that patients with vascular disease in these arteries have low blood flow and are at higher risk of stroke.

The study will enroll 80 patients at five sites who have first-time stroke symptoms caused by 50 percent or greater blockage of the arteries leading to the back of the brain.

Patients will receive standard brain imaging with MRI or CT, imaging of the blood vessels, and possible medication therapy, which might include aspirin, anti-cholesterol medication, or blood pressure lowering medication.

As part of the study, patients will additionally undergo magnetic resonance (MR) perfusion and quantitative magnetic resonance angiography (QMRA) that measures blood flow using NOVA technology developed by UIC neurosurgeon Dr. Fady Charbel. The Noninvasive Optimal Vessel Analysis measures the volume of blood flow, direction, and provides a four-dimensional view of the shape and form of blood flow.

Patients will be imaged when they are first enrolled in the study and six and 12 months later. They will be monitored monthly for any recurrent symptoms that would suggest a stroke.

After following the participants for a minimum of one year, researchers will compare the blood flow of patients who had a stroke since their initial symptoms with those patients who did not have stroke.

We hypothesize that patients who have better blood flow to their brains are going to be the ones that don't have new strokes, and those that have low blood flow on their brain scans will be at higher risk of having strokes, said Amin-Hanjani.

If this is demonstrated, then patients with low blood flow to their brain -- even when they first have stroke symptoms -- may be candidates for intervention such as stenting or angioplasty to increase blood flow, said Amin-Hanjani. At the same time, people who have stroke symptoms but normal blood flow could be reassured that their risk of stroke on medication therapy is low, and there may be no need for further intervention exposing them to unnecessary risk.

If we know who is at highest risk, we may be able to figure out who is going to benefit the most from interventional treatment, said Amin-Hanjani. Given that treatment such as stenting is not entirely risk free, it would be important to know that you're treating the highest risk population and offering them a benefit, rather than treating patients who may not need it.

Gabapentin may help recovering alcoholics

Mon, 04 Aug 2008 13:15:09 PST

( from http://www.rxpgnews.com ) People with alcohol problems often use alcohol to get to sleep -- but it actually keeps them from getting good-quality sleep all night long.

At the same time, they're highly likely to suffer from full-blown chronic insomnia that keeps them from getting enough sleep night after night – and that condition has been shown to cut their chances of getting sober again.

Meanwhile, their doctors aren't likely to prescribe them insomnia medications, because most sleeping pills can be habit-forming or have adverse effects due to an alcohol-damaged liver.

Now, a small new pilot study from a team of University of Michigan alcoholism and sleep researchers offers some sign of a possible way out of this conundrum.

The study, published in the August issue of the journal Alcoholism: Clinical and Experimental Research, suggests that the drug gabapentin might be able to reduce insomnia in recovering alcoholics, and help them stay away from alcohol more successfully. The drug, often used to treat epilepsy and chronic pain, is not habit-forming and is not processed by the liver.

Although the study involved only 21 insomniacs in recovery from alcohol dependence, and did not provide long-term gabapentin treatment or long-term follow-up on their sleep or their alcohol recovery, it was randomized, placebo-controlled, and double-blinded. In all, 30 percent of the patients who received gabapentin during alcohol recovery relapsed to drinking, compared with 80 percent of those who received a placebo.

Based on the results, the researchers have already launched additional studies of the potential role of gabapentin in alcohol recovery and sleep.

"We showed that the patients who got the real drug, rather than placebo, were less likely to relapse to drinking -- or if they relapsed it was later," says lead author Kirk Brower, M.D., FASAM, the executive director of U-M Addiction Treatment Services and a professor of psychiatry at the U-M Medical School. "In other words, gabapentin prevented and delayed relapse. Meanwhile, patients reported sleeping better in both the treatment and placebo groups, which may be due to the gabapentin in the first group and the resumption of drinking in the other."

Co-author Flavia Consens, M.D., an associate professor of neurology and member of the U-M Sleep Disorders Center, is cautiously optimistic that the new findings could open the door to better understanding of how to handle sleep problems in people who are trying to recover from their dependence on alcohol. As many as 70 percent of people with alcohol problems suffer insomnia, she says, while others cope with other sleep disturbances including breathing problems known as sleep apnea.

Nearly 14 million Americans meet the diagnostic criteria for alcohol abuse or alcoholism. Alcohol problems, alone or in combination with illicit drug problems, account for 40 percent of admissions to addiction treatment programs each year, according to the federal Substance Abuse and Mental Health Services Administration.

"There may be some underlying chemical changes in the brain that prompt alcoholics to report more insomnia as a co-existing condition than non-alcoholics," she says. "A possible explanation of these new findings is that the gabapentin might decrease the insomnia initially, and the patient may not need or crave alcohol as a treatment for the insomnia. We're also looking into other factors that may have an effect on the neurochemistry of the brain, and see how they could impact recovery and sleep."

The researchers caution that they did not observe differences in brain wave data collected during sleep studies conducted before and after patients received gabapentin. Neither did the drug appear to have a greater benefit for insomnia than placebo during the first 6 weeks of receiving study medication. Six weeks after stopping medication, however, those who had taken gabapentin reported worse insomina than those on placebo. Insomnia was measured using standardized questionnaires for a total of 12 weeks

All of the volunteers met national criteria for alcohol dependence, and were either in alcohol treatment or expressed a willingness to abstain from alcohol. They also all met criteria for insomnia that had lasted six months or more. They could not have other medical or mental health conditions, or be taking medications, that might affect their sleep, and underwent blood tests to rule out medical illnesses such as thyroid deficiency and liver disease.

Each of the study volunteers spent three nights in the U-M Sleep Disorders Center: two during the preparation for the study, and one three weeks after they began to receive gabapentin or placebo. All the volunteers received up to six brief sessions of behavioral therapy aimed not at sleep or alcohol issues, but rather at adherence to the study medication.

Fourteen of the volunteers successfully completed the entire study, including a follow-up appointment six weeks after they completed the six-week course of gabapentin or placebo, and three overnight sleep studies.

Brower notes that the medication dose and schedule used in the study may have contributed to the relatively weak effect on sleep that was seen from gabapentin. Patients took one dose each evening, rather than the three doses throughout the day that are routinely given for epilepsy or pain.

"These results raise more questions for us to explore, including the potential impact of gabapentin on people who are in recovery from alcohol dependence but do not report insomnia," he says.

Differences in swallowing mechanism of Rett syndrome patients

Mon, 04 Aug 2008 12:48:57 PST

( from http://www.rxpgnews.com ) Researchers at Wake Forest University Baptist Medical Center have found that the reflux and swallowing problems that are common symptoms in patients with Rett syndrome and other neurological impairments, may be caused by a different mechanism than they are in healthy individuals. The finding leaves researchers to wonder if these patients truly benefit from anti-reflux surgery commonly performed in these children.

In a study published in this quarter's issue of the Journal of Applied Research, John E. Fortunato, M.D., lead researcher and an assistant professor in the Department of Pediatrics, found that the esophagus of children with Rett syndrome demonstrates different movements than it does in patients without the neurological disorder, which may explain why so many Rett patients experience persistent reflux and swallowing issues even after undergoing surgery meant to correct those problems.

"The significance of this is for other groups of patients with neurological impairment," Fortunato said. "Do all of these patients have the same mechanism for reflux and swallowing disorders? If not, performing a fundoplication (anti-reflux surgery) may not help. In fact, it may make things worse like it did in the Rett girls."

Previous studies have shown that children with neurological impairments have increased complications after anti-reflux surgery. In this study, Fortunato found the same to be true of Rett syndrome patients who underwent fundoplication. The finding leads researchers to believe that there may be something different causing the reflux and swallowing problems in Rett syndrome patients and possibly other patients with neurological impairments, such as cerebral palsy, brain injury and autism, than the accepted mechanism for the same problems in otherwise healthy adults and children.

Rett syndrome is a childhood neurodevelopmental disorder caused by mutations in the gene MECP2 located on the X chromosome. It is the only Autism spectrum disorder with a known genetic cause and is characterized by normal early development followed by loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, walking abnormalities, seizures, and mental retardation. Early symptoms may also include toe walking, sleep problems, teeth grinding, difficulty chewing and breathing difficulties while awake such as hyperventilation, apnea (breath holding), and air swallowing.

Rett syndrome affects one in every 10,000 to 20,000 live female births and is associated most closely with gastroesophageal reflux disease (GERD) and difficulty and /or pain swallowing (dysphagia). Most patients affected by the mutation have trouble eating, so they often are shorter and weigh less than other children their age. To maintain proper nutrition, some children need to be fed through tubes placed in their noses or stomachs. Boys who inherit the mutated gene usually don't survive infancy, according to the National Institute of Neurological Disorders and Stroke.

The study included 32 Rett patients between the ages of 2 and 14 with prior history of feeding problems. Researchers looked at the movement (or peristalsis) of the esophagus in the girls and found unusual esophageal movement disorders.

As a result of the study's findings, Wake Forest Baptist has approved further research to look at esophageal movement and swallowing function before and after reflux surgery, comparing children with and without neurological impairment.

"This issue is of particular interest to pediatricians who refer these patients for their 'reflux' problems," Fortunato said. "If we develop a better understanding of the mechanisms behind the problems being experienced by these children, we just might be able to find a way to make life a little more comfortable for them."

Topiramate may increase the risk of birth defects

Tue, 22 Jul 2008 10:41:00 PST

( from http://www.rxpgnews.com ) Taking the epilepsy drug topiramate alone or along with other epilepsy drugs during pregnancy may increase the risk of birth defects, according to a study published in the July 22, 2008, issue of Neurology®, the medical journal of the American Academy of Neurology.

Research has shown that many epilepsy drugs increase the risk of birth defects, but little research has been done on topiramate. Studies have shown that topiramate increases the risk of birth defects in animals. Maintaining effective epilepsy treatment during pregnancy is crucial because seizures may cause harm to the fetus.

For the study, researchers examined women who became pregnant while taking topiramate either on its own or along with other epilepsy drugs. Of 178 babies born, 16 had major birth defects. Three of these were in infants whose mothers were taking only topiramate, and 13 were in those whose mothers were taking topiramate and other epilepsy drugs.

Four of the babies had cleft palates or cleft lips, a rate 11 times higher than that expected if these women were not taking epilepsy drugs. Four male babies had genital birth defects, with two of those classified as major defects, which is 14 times higher than the normal rate for this defect.

"More research needs to be done to confirm these results, especially since it was a small study," said John Craig, MRCP, of the Royal Group of Hospitals in Belfast, Northern Ireland. "But these results should also get the attention of women with migraine and their doctors, since topiramate is also used for preventing migraine, which is an even more common condition that also occurs frequently in women of childbearing age."

Craig said the risk of birth defects may be different for women taking the drug for migraine, but that the pregnancies of women exposed to topiramate should be monitored.

This study found that more birth defects occurred in women taking topiramate along with the drug valproate, or valproic acid, than in women taking topiramate and another epilepsy drug. Research has shown that valproate is associated with a high risk of birth defects.

Ventricle size increase prior to Alzheimers diagnosis

Sat, 12 Jul 2008 03:51:36 PST

( from http://www.rxpgnews.com ) Researchers at Robarts Research Institute at The University of Western Ontario have found clear evidence that increases in the size of the brain ventricles are directly associated with cognitive impairment and Alzheimer’s disease.
Ventricles are fluid-filled cavities in the brain. The research, led by Robarts scientist Robert Bartha, shows the volume of the brain ventricles expands as surrounding tissue dies. The research was published online today in the neurology journal Brain.

Currently, diagnosis for Alzheimer’s relies on neuro-cognitive assessments, such as testing of memory, ability to problem solve, count, etc. Definitive diagnosis is not possible until after death when an autopsy can reveal the presence of amyloid plaques and ‘tangles’ in brain tissue.

Previous research has shown the link between ventricle size and Alzheimer’s over longer time intervals. The research conducted at Robarts Research Institute shows that ventricle size increases with mild cognitive impairment before a diagnosis of Alzheimer’s disease, and continues to increase with the onset and progression of Alzheimer’s disease after only six months.

“These findings mean that, in the future, by using magnetic resonance imaging (MRI) to measure changes in brain ventricle size, we may be able to provide earlier and more definitive diagnosis,” said Bartha, who is also an Associate Professor in the Schulich School of Medicine & Dentistry in Medical Biophysics. “In addition, as new treatments for Alzheimer’s are developed, the measurement of brain ventricle changes can also be used to quickly determine the effectiveness of the treatment.”

The research also showed that Alzheimer’s patients with a genetic marker for Alzheimer’s disease exhibited faster expansion in ventricle volume.

The research was performed by utilizing MRI scans from individuals from across North America. Graduate student Sean Nestor, a coauthor, examined 500 data sets of individuals at baseline and six months later. The images were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large multi-site trial sponsored by the National Institutes of Health in the United States and the pharmaceutical industry. The project includes an online database of imaging information gathered from 800 people at more than 50 sites across the U.S. and Canada. The images are MRIs of individuals with no cognitive impairment, those with mild cognitive impairment and people with Alzheimer’s disease. The database can be used by any primary researcher.

One of the ADNI sites is at London’s Lawson Health Research Institute, and is led by Dr. Michael Borrie, a co-investigator on the research. Dr. Borrie is Medical Director of the Aging Brain and Memory Clinic and Geriatric Clinical Trials Group at Parkwood Hospital, St. Joseph’s Health Care, London, a Lawson researcher and Chair of the Division of Geriatric Medicine at Western’s Schulich School of Medicine & Dentistry.

Examination of the MRIs was made possible by using software developed by Cedara Software, the OEM division of Merge Healthcare. In the past, researchers would have to manually or semi-automatically trace the ventricles in many brain images, each showing a “slice” of the brain. The Merge OEM software team, led by Vittorio Accomazzi, a coauthor in the research, worked closely with the researchers to refine the software to allow the processing of large volumes of data very quickly.

"This is one of the first major research studies published using data from ADNI", said Borrie, "but there will be many more neuroimaging and biomarker discoveries to arise from the ADNI project. It is a tremendous opportunity for researchers anywhere in the world to use the ADNI databases, to collaborate and share their findings in a new way that will move Alzheimer's disease research forward more quickly, objectively and effectively. Already we are building new international collaborations, arising from ADNI, that we could not have even imagined."

Stem cell restore muscle in mice with muscular dystrophy

Sat, 12 Jul 2008 03:15:05 PST

( from http://www.rxpgnews.com ) By injecting purified stem cells isolated from adult skeletal muscle, researchers have shown they can restore healthy muscle and improve muscle function in mice with a form of muscular dystrophy. Those muscle-building stem cells were derived from a larger pool of so-called satellite cells that normally associate with mature muscle fibers and play a role in muscle growth and repair.

In addition to their contributions to mature muscle, the injected cells also replenished the pool of regenerative cells normally found in muscle. Those stem cells allowed the treated muscle to undergo subsequent rounds of injury repair, they found.

"Our work shows proof-of-concept that purified muscle stem cells can be used in therapy," said Amy Wagers of Harvard University, noting that in some cases the stem cells replaced more than 90 percent of the muscle fibers. Such an advance would require isolation of stem cells equivalent to those in the mouse from human muscle, something Wagers said her team is now working on.

Satellite cells were first described decades ago and have since generally been considered as a homogeneous group, Wagers said. While anatomically they look similar under a microscope, they nonetheless show considerable variation in their physiology and function. In a previous study, Wagers' identified a set of five markers that characterize the only subset of satellite cells responsible for forming muscle, which they also refer to as skeletal muscle precursors or SMPs.

In the new study, the researchers analyzed the stem cell and regenerative properties of those SMPs. When engrafted into muscle of mice lacking dystrophin, purified SMPs contributed to up to 94 percent of muscle fibers, restoring dystrophin expression and significantly improving muscle structure and contractile function, they report. (The dystrophin gene encodes a protein important for muscle integrity. Mice lacking dystrophin, also known as mdx mice, are a model for Duchenne Muscular Dystrophy, the most prevalent form of muscular dystrophy.)

" Importantly, high-level engraftment of transplanted SMPs in mdx animals shows therapeutic value—restoring defective dystrophin gene expression, improving muscle histology, and rescuing physiological muscle function," the researchers said. "Moreover, in addition to generating mature muscle fibers, transplanted SMPs also re-seed the satellite cell niche and are maintained there such that they can be recruited to participate in future rounds of muscle regeneration.

"Taken together, these data indicate that SMPs act as renewable, transplantable stem cells for adult skeletal muscle. The level of myofiber reconstitution achieved by these myogenic stem cells exceeds that reported for most other myogenic cell populations and leads to a striking improvement of muscle contraction function in SMP-treated muscles. These data thus provide direct evidence that prospectively isolatable, lineage-specific skeletal muscle stem cells provide a robust source of muscle replacement cells and a viable therapeutic option for the treatment of muscle degenerative disorders."

Wagers noted however that there may be complications in the delivery of cell therapy in humans, particularly for those with conditions influencing skeletal muscle throughout the body. Even so, the new findings present an "opportunity to understand what happens [to these regenerative cells] in disease and identify factors and pathways that may boost their activity," she said. "We may get a handle on drugs that could target muscle impairment" not only in those with muscular dystrophies, but also in elderly people suffering from the muscle wasting that comes with age.

Mechanism for Parkinsonian tremor found

Sat, 12 Jul 2008 03:07:38 PST

( from http://www.rxpgnews.com ) A typical symptom of Parkinson's disease is tremor in patients. A group of scientists, including Professor Peter Tass from Forschungszentrum Jülich have succeeded in demonstrating the mechanisms which cause the so-called tremor: neuron clusters in the depths of the brain drive the tremor. This discovery supports Tass' research activities aiming at developing a therapy for Parkinson's disease. A new deep brain pacemaker is to bring cells out of the diseased mode for good.

A recent article article in the high-impact journal "Europhysics Letters" shows that the scientists from Forschungszentrum Jülich, a member of the Helmholtz Association, are on the right track. Their new deep brain pacemaker is to help Parkinson's patients on a large scale for the first time in 2009. Communication between the networks of neurons is disturbed in people suffering from Parkinson's disease. These "fire" their stimuli at the same time thus causing the typical tremor. The frequency measured here is 5 hertz (Hz), i.e. five oscillations per second. In Germany, there are officially around 150,000 Parkinson's patients, although it is estimated that up to 450,000 people are affected.

To date, scientists have assumed that the 5-Hz rhythm deep in the brain resulted from nerve signals, which are transmitted from muscles in the limbs back to the brain. The scientific term for this response is "proprioceptive feedback". The prevailing opinion of many scientists to date, however, is that the "cross fire" is not emitted by the brain. The reason for this assumption was that the measured frequency of the "proprioceptive feedback" and the frequency in a specific core region of the brain, in the thalamus and the basal ganglia, were not completely synchronous.

With a combination of several state-of-the-art analytical processes, the team has now succeeded in demonstrating that it is not only nerve signals from the muscles as feedback that drive the diseased 5-Hz rhythm in the brain. Headed by Prof. Volker Sturm, neurosurgeons in Cologne implanted electrodes in patients for the measurements, and scientists in Saratov, Russia, recalculated the obtained data together with scientists from Jülich. "Signals in the frequency domain of 5 Hz from the core region of the brain also drive the tremor", explained Peter Tass. "The difference: the feedback from the limbs is a fast and easy stimulus transmission. The signals from the thalamus and the basal ganglia are, however, transmitted to certain loop-like neuron pathways of the brain and spinal cord. Therefore, the dynamics are more complicated and the pathway is longer."

The Jülich medical scientist, mathematician and physicist believes that these new findings reinforce the theoretical basis of "his" deep brain pacemaker. This device influences the disturbed neurons in the core region of the brain and effectively removes their compulsion to "fire" at the same time. Tass' new development disturbs this compulsory diseased mode by using very mild, targeted and desynchronized stimuli in different places. In this way, the rhythm becomes irregular and breaks down. Compared to conventional devices of this type, the Jülich deep brain pacemaker puts less strain on the patient and needs less energy. Moreover, the nerve tissue is stimulated in such a way that the neurons abandon their diseased strong synaptic networks and thus forget their compulsion to develop diseased rhythms.

The pacemaker consists of two electrodes that are carefully located at the dysregulated parts of the brain. The so-called stimulator provides the electrodes with energy and signals to stimulate the neurons in the brain. This device is implanted below the collarbone under the skin and thin wires also connect it with the electrodes under the skin.

Japanese encephalitis virus causes 'double trouble' to brain

Mon, 07 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Japanese encephalitis (JE), commonly known as brain fever, is one of the prevalent mosquito-borne encephalitis in India and entire South East (SE) Asia. Besides resulting in thousand fatalities each year, JE virus (JEV) infection causes prominent neurological sequelae in approximately one-third of the survivors. Even those patients in the good recovery group commonly encounter psychiatric problems, which include mental retardation, learning disabilities, speech and movement disorders and behavioural abnormalities.

Recent research in National Brain Research Center, Manesar, India by Dr. Anirban Basu and his graduate student, Sulagna Das have shown that JE virus damages the brain in two ways, by not only killing brain cells but by preventing the birth of new cells from neural stem/progenitor cells (NPC) and depleting the NPC pool in the brain. It's a double hit to the brain, the JE virus causes brain injury by killing neurons as well as prevents its repair lead researcher and the senior author of the work Anirban Basu said in a statement.

The children are more vulnerable targets of this virus, which causes massive neuronal loss in the Central Nervous System. Children are at a dynamic stage of brain development, hence infection at this stage can have devastating effects on mental functions later in life. Our study has tried to explore how JEV infection leads to development of long-term cognitive deficits in the survivors, says Dr. Anirban Basu who has been working in the neurobiology of JEV infection for the past 4 years. These findings have been published online in a paper in Journal of Neurochemistry for inclusion in a future issue of the journal.

The breakthrough here is that the JE virus prevents neural stem and progenitor cells in the brain from dividing; it hangs them up, Basu said. It's the first time that a mosquito-borne virus has ever been shown to affect neural stem cells. The progressive infection in these cells eventually results in decrease in proliferation ability, providing a possible explanation for their diminished pool upon infection, said Basu. He also went on to state, The neurological and cognitive deficits in the JE survivors could be related to the drop in NPC cells in the neurogenic region of the brain called the subventricular zone.

Neural stem/progenitor cells are the saviours of the brain following any insult or infection and via the process of neurogenesis help the recovery process. These cells have the ability to self-renew over lifetime and generate both neurons and glia, which make up the CNS. The initial work with neural stem cells in cell culture dishes interestingly showed that unlike neurons, these stem cells are a resilient population and do not undergo robust cell death upon JEV infection. Instead, the virus lowers the NPC pool by disrupting the growth kinetics and the proliferative ability of these cells. The study was extended in mouse models of JE, where a significant decrease in the actively proliferating NPCs was observed in the subventricular zone or the primary niche of post-natal neurogenesis.

The possible mechanism by which JEV reduces the proliferating NPC pool was also worked out by the scientists utilising the cell cycle studies. Sustained proliferation is a key feature of NPCs, which have to pass through various cell cycle checkpoints and phases of division. Upon JEV infection, these cells halt at the resting phase and fail to proceed to the dividing S-phase. Both cell culture and animal studies indicate that JEV inhibits the DNA synthesis in these cells during progressive infection and induces cycle arrest in them. The researchers went on to show that the virus leads to increased expression of certain checkpoint proteins that block the transition of cells to S-phase, thus preventing the NPCs from multiplying.

Over the years, JE has become a major cause of mortality and morbidity in wide areas of SE Asia. The very high incidence of permanent and disabling neurological sequelae has considerable socioeconomic impact. Knowing the mechanism, we can start to approach this therapeutically Basu said. This indicates that we might eventually treat this form of neurological and psychiatric problems by either ramping up brain repair or protecting the repair mechanism, Das added.

Spreading depolarisation after a stroke- warning sign

Thu, 12 Jun 2008 10:05:43 PST

( from http://www.rxpgnews.com ) After a stroke, even unaffected areas of the brain are at risk – depolarization waves arise at the edges of the dead tissue and spread through the adjacent areas of the brain. If these waves are repeated, more cells die. This has previously been observed only in animal studies.

A clinical study at the university hospitals of Heidelberg and Cologne along with the Max Planck Institute of Neurological Research in Cologne has shown for the first time that this phenomenon occurs after a stroke in humans and is a warning sign that more nerve cells will die. The study, published in June 2008 in the renowned journal “Annals of Neurology,” may allow to translate more than 60 years of experimental research for the diagnosis and therapy of stroke patients.

More than 150,000 people a year in Germany suffer a cerebral stoke, the third most frequent cause of death in industrialized countries. When deposits clog vessels to the brain, some areas of the brain do not receive sufficient oxygen and the tissue dies. Depending on the size of the area affected, the patients may die or suffer permanent damage such as paralysis.

Spreading depolarizations first proven in stroke patients

The depolarization waves in the brain – known as cortical spreading depression (CSD) – have been studied only experimentally since the 1940s. Many features are thus known from animals – the waves of depolarization that can spread out at a speed of two to five millimeters per minute are followed by silence – brain activity comes to a halt for a short time. In this time, the nerve cells recover. “The impact of these waves is several times greater for nerve cells than an epileptic seizure,” says Professor Dr. Rudolf Graf from the Max Planck Institute of Neurological Research and co-founder of the international study group COSBID (Cooperative Study on Brain Injury Depolarisations).

“After the stroke, circulation in the tissue surrounding the affected area of the brain is initially poor, but it can still be saved,” explained Dr. Christian Dohmen of the Neurology Department at Cologne University Hospital. The spreading depolarizations additionally impair the metabolism of the weakened nerve cells. “The more frequently such waves occur, the longer the nerve cells require to recover, until finally they die off entirely,“ says the main author of the study. To what extent the brain is damaged after a stroke depends thus on the number of these spreading depolarizations. This correlation is becoming apparent in humans as well.

Know-how from 60 years of research can now be used for treating stroke patients

The spreading depolarizations, which also occur after head injuries or hemorrhages, can be measured only on the surface of the brain. For this study, the physicians therefore selected 16 patients whose brain had to be partially exposed due to a life threatening swelling of brain tissue. Electrodes were applied to the surface of the brain around the affected tissue (electrocorticography), the incisions were closed, and brain waves were measured for five days. All patients were in an artificial coma during this period due to their serious condition.

"Our study puts an end to the discussion as to whether these waves also occur in a human brain following a stroke,“ says Dr. Oliver Sakowitz, physician at the Department of Neurosurgery of the University of Heidelberg Hospital and co-author of the study. Now comes the question of how to prevent or at least contain them. “As they cause additional damage to the weakened tissue surrounding the stroke area, it is conceivable that we could prevent further damage by suppressing the waves,” said the neurosurgeon.

In previous experimental studies on animals, a few therapy approaches were already developed which physicians can now apply. “The spreading depolarizations are a warning sign that other areas of the brain are at immediate risk and may be also useful as diagnostic measures,” says Dr. Sakowitz. In a follow-up study on a larger number of stroke patients, the COSBID team under the direction of Dr. Christian Dohmen wants to clarify whether cortical spreading depression has an influence on the extent of sequelae such as paralysis.

Anti-estrogen drug therapy reduces risk of invasive breast cancer in older women

Tue, 10 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) New analysis of a drug approved for osteoporosis prevention and treatment has provided definitive evidence that the medication is also effective as a breast cancer preventative for certain cancers. Women who took the drug raloxifene were less likely to develop invasive, estrogen-receptor (ER) positive breast cancer compared with women who did not take the drug. The results of the randomized controlled trial will be published in the June 10 online issue of the Journal of the National Cancer Institute.

Breast cancer is the most common cancer among women. In 2008, to date, 182,460 new cases of female breast cancer have been diagnosed and 40,480 women have died due to breast cancer (National Cancer Institute).

Raloxifene is a selective estrogen receptor modulator (SERM), which means that the drug has estrogen-like effects on some tissues, such as bone, but anti-estrogen effects on other tissues such as breast. Previous data from the RUTH (Raloxifene Use for The Heart) Trial, which involved more than 10,000 post-menopausal women participants around the world who had an increased risk of coronary heart disease, showed that the drug did not protect against heart disease but it did reduce the risk of invasive breast cancer by 44 percent. The drug is currently approved by the FDA for the prevention and treatment of osteoporosis in postmenopausal women, and invasive breast cancer risk reduction in postmenopausal women with osteoporosis or at high risk for breast cancer.

In this paper, researchers report that, regardless of age, prior hormone use or baseline breast cancer risk, raloxifene reduced the risk of hormone responsive (ER-positive) breast cancers by at least 50 percent for at least 8 years. Most postmenopausal women with breast cancer have this kind of breast cancer.

Non-invasive cancers confine themselves to the ducts or lobules and do not spread to the surrounding tissues in the breast or other parts of the body. They can, however, develop into or raise the risk for a more serious, invasive cancer. Invasive cancers are more aggressive and have started to break through normal breast tissue barriers and invade surrounding areas.

This research gives older women facing certain medical decisions another option, explained principal investigator Elizabeth Barrett-Connor, M.D., distinguished professor and Chief, Division of Epidemiology, Department of Family and Preventive Medicine, and a member of the Cancer Prevention and Control Program, UC San Diego School of Medicine. For example, if a woman at risk for osteoporosis is considering taking medication, and has no history of blood clots or stroke, raloxifene might be a more appealing option due to its protective role in invasive breast cancer.

The RUTH trial, the world's largest study of women and heart disease, was a randomized, blinded, placebo-controlled trial conducted at 177 sites, in 26 countries, on five continents. Between June 1998 and August 2000, 10,101 postmenopausal women with coronary heart disease or several heart disease risk factors were randomly assigned to raloxifene or to placebo and followed for a median of 5.6 years. The 5,044 women who took raloxifene had a 55 percent reduction in risk of developing invasive ER-positive breast cancer as compared to the 5,057 women who took placebo.

The initial results of the RUTH trial were published in 2006. The reduction in breast cancer risk was consistent with findings from other trials that involved women who did not have heart disease. However, women who took raloxifene in the RUTH trial had an increased incidence of blood clots and fatal strokes compared to those who took placebo. Thus, the researchers concluded that women considering use of raloxifene need to weigh the risks and benefits.

Study author Deborah Grady, M.D., M.P.H., of the University of California, San Francisco, and colleagues examined the RUTH trial data in more detail in order to investigate the specific types and stages of breast cancer affected by raloxifene, as well as the timing of its action and the types of patients it can help.

In this study, we looked at whether raloxifene would be more effective in some subgroups of women than others, but found that the relative benefit was the same, regardless of breast cancer risk, said Grady. Like any therapy, the risk needs to be balanced with the side effects, which for raloxifene include blood clots and fatal stroke.

But these findings are important because few drugs actually reduce the risk of breast cancer. noted Grady. Also raloxifene has been on the market for nearly a decade with good, long term safety data, said Barrett-Connor.

Researchers say women who would have the best risk-benefit ratio would be those at high risk of breast cancer, who have a 30 to 50 percent chance of getting breast cancer in the next five to ten years, and low risk of venous thrombosis and stroke. A reduced risk of spine fractures would be an additional benefit.

Study identifies brain pathway that shuts down seizures

Sun, 08 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at the University of Iowa and the Veterans Affairs Iowa City Health Care System have uncovered a brain pathway that shuts down seizures.

The multidisciplinary team of scientists pieced together information from clinical observations made in the first half of the 20th century with knowledge from modern genetics and molecular biology to show that an acid-activated ion channel in the brain reacts to a drop in pH (increased acid) in a way that shuts down seizure activity.

The link between low pH in the brain and seizure termination was first hinted at nearly 80 years ago when clinical experiments showed that breathing carbon dioxide, which makes brain tissue more acidic, helps stop epileptic seizures. Subsequent studies in the 1950s found that seizures themselves reduce brain pH. However, it was the modern discovery of an acid-activated ion channel (ASIC1a) in the brain that provided the key to the UI discovery, which is reported in Nature Neuroscience Advance Online Publication on June 8.

We found that ASIC1a does not seem to play a role in how a seizure starts, but as the seizure continues and the pH is reduced, ASIC1a appears to play a role in stopping additional seizure activity, said Adam Ziemann, a student in the Medical Scientist Training Program at the UI and co-lead author of the study.

Specifically, the study shows that mice without the ASIC1a gene have more severe and longer seizures than mice with the gene. In addition, chemically blocking ASIC1a increases the severity and duration of seizures in mice with the gene. Conversely, increasing the expression of ASIC1a in mice protects the animals from severe seizures.

The team also showed that reducing the pH in slices of brain tissue expressing ASIC1a reduced seizure activity, but acid had no effect on seizures in tissue without the protein.

When the team measured pH in mouse brains, they showed that seizures lower the pH to levels that can activate ASIC1a channels. They also found that breathing carbon dioxide causes an additional rapid drop in brain pH, and that breathing 10 percent carbon dioxide was sufficient to protect mice with the ASIC1a protein from lethal seizures.

In seizures, ASIC1a appears to be activating inhibitory neurons, explained John Wemmie, M.D., Ph.D., senior study author and assistant professor of psychiatry in the UI Roy J. and Lucille A. Carver College of Medicine, and a staff physician and researcher at the VA Iowa City Health Care System. This is the first study to show that ASIC1a activation can have an inhibitory effect.

One of the most exciting aspects of the work is that it highlights the potent anti-epileptic effects of acid in the brain -- effects that have been recognized for nearly 100 years but until recently have been poorly understood -- and it identifies ASIC1a as a key player in mediating the anti-epileptic effect of low pH, Ziemann said.

We don't know yet, but presumably there might be examples where the seizures don't stop because of a deficit in this pathway, Wemmie added.

Seizures involve abnormal synchronous firing of groups of neurons, which can cause physical symptoms such as spasms or convulsions and, in the most serious cases, altered control of vital bodily functions, like breathing. Approximately 2 to 4 percent of people will have a seizure at some point in their lives. People who have epilepsy experience repeated seizure activity.

Although the vast majority of seizures are self-limiting and stop by themselves, seizures that don't stop can develop into a life-threatening condition called status epilepticus with a mortality rate of up to 20 percent.

The discovery helps explain why breathing carbon dioxide stops seizures, which might stimulate the use of carbon dioxide for stopping seizures, Wemmie said. However, although this work provides insight into how seizures normally stop and might help us learn more about how to terminate those seizures that don't stop, it will take more work to turn the finding into a new therapeutic approach. We will be working with colleagues in neurology and neurosurgery to try and translate the findings to treatments.

Ziemann noted that a particular strength of neuroscience research at the UI is the close interaction between faculty doing cutting-edge human studies and those pursuing basic science.

New guidelines for treating resistant hypertension

Fri, 06 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) BIRMINGHAM, Ala. -- Resistant hypertension, blood pressure that remains above goal despite taking three antihypertensive medications or high blood pressure that is controlled but requires four or more medications to do so, may benefit from specialized diagnostic and therapeutic treatment by health care providers according to guidelines issued by the American Heart Association and co-authored by UAB physicians.

Lead author David A. Calhoun, M.D., professor of medicine in the UAB Division of Cardiovascular Disease, and colleagues said successfully treating resistant hypertension requires patients to modify lifestyle factors that contribute to treatment resistance, including using less salt, losing weight and drinking less alcohol. It also requires physicians to better diagnose and treat secondary causes of high blood pressure and more effectively use multiple-drug treatments. This is the first consensus statement to define resistant hypertension and recommend an approach for evaluation and treatment.

Calhoun said while it is not known how many people in the U.S. with high blood pressure have resistant hypertension clinical trials suggest it may as high as 20 to 30 percent.

Older age and obesity are two of the strongest risk factors associated with resistant hypertension and unfortunately, with an aging and increasing heavy population, we can anticipate resistant hypertension becoming more and more common, he said. And people need to recognize the importance of blood pressure control. Persons with resistant hypertension are at increased risk for cardiovascular diseases, including heart attacks and strokes.

Calhoun and colleagues emphasize in the statement that effective use of diuretics is essential for treatment of resistant hypertension. Calhoun said they recommend that a long-acting diuretic be part of the treatment regimen of all patients with resistant hypertension in order reduce fluid retention and thereby blood pressure. He added that some patients may also benefit from adding mineralocorticoid receptor antagonists (MRAs) to their treatment regimens. MRAs have traditionally been used to treat a condition called primary aldosteronism, which is found in about 20 percent of patients with resistant hypertension. However, recent clinical studies indicate that MRAs may be useful in treating resistant hypertension even in the absence of demonstrable aldosterone excess.

The benefit of MRAs for treating resistant hypertension has been recently appreciated, he said. Hypertension specialists are using them more commonly, but they are probably not being routinely used by other physicians. Prescription of MRAs does require biochemical monitoring, particularly measurement of serum potassium levels, which does limit there use.

Calhoun said it is important to note that uncontrolled high blood pressure and resistant hypertension are not the same and effectively evaluating a patient to distinguish between the two possibilities is key to successful treatment.

High blood pressure readings can be caused by poor medication adherence, which is not the same as resistant hypertension, he said. Confirming treatment resistance is the first step in evaluating difficult-to-treat high blood pressure. It also is important to evaluate the condition correctly because often, patients with resistant hypertension have other medical conditions that complicate their blood pressure management. If a secondary cause of hypertension is identified such as obstructive sleep apnea, renal parenchymal disease, primary aldosteronism or renal artery stenosis, treating these disorders, which may require referral to a specialist, can improve blood pressure control.

USC awareded $12.4 million to spearhead stroke survivors rehabilitation project

Fri, 06 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) The University of Southern California is taking the lead to address rehabilitation therapy and how it can improve the quality of life for stroke survivors. Each year, about 700,000 people in the United States experience first or recurrent attacks of stroke.

About 65 percent of stroke survivors experience significant disability, such as the loss of use of one arm. This can lead to a reduced quality of life and loss of independence, says Carolee Winstein, director of the Motor Behavior and Neurorehabilitation Laboratory at USC.

More effective rehabilitation treatments could lessen the disability, caregiver burden and economic impact of stroke, says Winstein, a professor of biokinesiology and physical therapy.

To address the problem, the NIH-National Institute of Neurological Disorders and Stroke and the NIH-National Institute of Child Health and Human Development awarded Winstein $12.4 million for a five-year study of a promising physical therapy program for stroke patients who have lost movement in their upper limbs.

The trial will investigate the effectiveness of the Accelerated Skill Acquisition Program (ASAP), an intense and focused outpatient rehabilitation program that emphasizes activities-based training and resistance exercises, and includes 30 hours of one-on-one therapy early in the rehab process, within the first three months of the stroke. The ASAP program also uses motivational techniques to encourage patients to self-manage their therapy.

Patients in the study will be divided into three groups; the ASAP therapy group, an outpatient group receiving a similar amount of PT and a monitoring only out-patient therapy group. The ASAP and outpatient group will attend a one hour therapy session, three times a week for 10 weeks. Meanwhile, the monitoring only group will receive out-patient therapy for a frequency and duration prescribed by their referring physician.

Winstein's study is named I-CARE, for Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (I-CARE) Stroke Initiative.

The I-CARE trial will link the USC School of Dentistry's Division of Biokinesiology and Physical Therapy with two other academic clinical research centers in the U.S.: the National Rehabilitation Hospital in Washington, D.C., led by co-principal investigator Alexander Dromerick, and the Emory University Center for Rehabilitation Medicine in Atlanta, Ga., led by co-principal investigator Steven Wolf. USC will serve as the primary project site and data management center.

I-CARE will also involve five Southern California physical rehabilitation sites: Cedars-Sinai Medical Center in Los Angeles, Casa Colina Centers for Rehabilitation in Pomona, Huntington Rehabilitation Medicine Associates in Pasadena, Long Beach Memorial Medical Center in Long Beach and Rancho Los Amigos National Rehabilitation Center in Downey.

The extensive study is expected to generate a wealth of useful data about stroke rehabilitation that could find use in trials of current and future experimental interventions such as pharmacological agents, gene therapy, stem cell implants and robot-assisted and direct cortical stimulation programs, Winstein says.

Researchers have discovered how an antibiotic works to modulate the activity of a neurotransmitter that regulates brain functions

Sun, 11 May 2008 01:12:33 PST

( from http://www.rxpgnews.com ) Virginia Commonwealth University researchers have discovered how an antibiotic works to modulate the activity of a neurotransmitter that regulates brain functions, which eventually could lead to therapies to treat Alzheimer’s disease, Huntington’s disease, epilepsy, stroke, dementia and malignant gliomas.

Neurodegenerative diseases are caused by the deterioration of neurons in the brain and spine resulting in problems related to either movement or memory. For most patients, it may be months or years before symptoms are evident because a large number of neurons die or stop functioning over a period of time. Currently, there are few treatment options for stopping this degeneration, and those currently being evaluated have shown minimal or no beneficial activity.

Paul B. Fisher, M.Ph., Ph.D., a professor and interim chair of the Department of Human and Molecular Genetics, and director of the VCU Institute of Molecular Medicine, in the VCU School of Medicine, and colleagues recently reported on the mechanism of action of ceftriaxone, a third-generation antibiotic with neuroprotective properties, in glutamate transport. The findings, published in the May 9 issue of the Journal of Biological Chemistry, suggest that this antibiotic or a similar drug may serve as a potential therapy against neurodegenerative disease caused by glutamate toxicity.

Glutamate is an amino acid that is important in nerve transmission and the synapse - the region that connects one neuron to another in the brain. When an excess of glutamate collects in the synapse, the result is glutamate toxicity or excitotoxicity. Ultimately, if glutamate is not cleared out of the synapse, neurons become damaged and die by a process called excitotoxicity. In previous studies, Fisher’s team identified ceftriaxone as a potent physiological stimulator of glutamate transport both in cell culture and in animal models.

“Glutamate excitotoxicity is a very important and fundamental process in neurodegeneration,” said Fisher. “Finding molecules, such as ceftriaxone, that may correct this problem can lead to preservation and increased survival of neurons in the brain and it may have direct implications in the therapy of many neurodegenerative diseases, such as in Alzheimer’s disease, stroke, ALS and epilepsy.”

In this study, Fisher and his colleagues were interested in identifying how the promoter region of the EAAT2 gene controlled the expression of glutamate in a group of brain cells called astrocytes. Using molecular biological approaches, the team examined all the regions and sequences in the promoter region and systematically eliminated them to then define which region was necessary to respond to ceftriaxone.

According to Fisher, this led the team to a critical transcription factor called nuclear factor kappaB, NF- kappaB, which regulates many functions in the brain and other parts of the body. This is a central molecule involved in regulation of genes controlling cell growth and survival. Once they identified critical regions in the EAAT2 promoter that might regulate activity, they found that alteration of one specific NF-kappaB site by mutation in the promoter was responsible for up-regulation of EAAT2 expression and consequently glutamate transport by ceftriaxone.

“This work not only has implications for the field of neurodegeneration and neurobiology, but may also help us more clearly understand brain cancer, including malignant glioma, an invariably fatal tumor, and how it impacts brain function,” said Fisher, who is the first incumbent of the Thelma Newmeyer Corman Endowed Chair in Cancer Research and researcher with the VCU Massey Cancer Center.

Future studies will examine ways to modify the structure of ceftriaxone through medicinal chemistry to create molecules that are pharmacologically improved. Currently, ceftriaxone needs to be injected, which is not the ideal for patient therapy, however, the development of an oral form would be a more preferential way to treat patients.

High blood urate slows progrssion of Parkinson's Disease

Mon, 14 Apr 2008 13:47:26 PST

( from http://www.rxpgnews.com ) Higher blood levels of the compound urate, a salt derived from uric acid that is associated with gout, may be associated with a slower progression of Parkinson’s disease, according to an article posted online today that will appear in the June 2008 print issue of Archives of Neurology, one of the JAMA/Archives journals.

Urate is a powerful antioxidant that circulates at high levels in the human bloodstream, according to background information in the article. It may serve as one of the body’s major defenses against oxidative stress, or damage to cells caused by nitrogen and oxygen. Oxidative stress may contribute to the loss of brain cells that produce dopamine, leading to Parkinson’s disease and other neurodegenerative disorders.

Michael A. Schwarzschild, M.D., Ph.D., of Massachusetts General Hospital, Boston, and colleagues studied 804 individuals with early Parkinson’s disease who were enrolled in a drug trial conducted between April 2002 and August 2005. Participants’ blood urate levels were measured at the beginning of the study. They were then seen one month later and again every three months until 24 months had passed. At each visit, they were clinically assessed to determine if their disease had progressed enough to require dopaminergic therapy.

Overall, 493 participants (61 percent) became disabled enough by their Parkinson’s disease to require dopaminergic therapy by the end of the study. Patients with high blood urate levels were less likely to progress to this point. When participants were separated into five groups based on their blood levels of urate, those in the group with the highest levels (6.7 milligrams per deciliter or higher) were half as likely to require dopaminergic therapy as those with the lowest levels (less than 4.3 milligrams per deciliter).

The apparent association between urate levels and Parkinson’s disease progression could indicate that urate itself protects dopamine-producing neurons that are typically destroyed as the condition worsens, the authors note. Alternatively, other compounds that the body eventually turns into urate could be neuroprotective.

“Measurement of urate on its own in patients with newly diagnosed Parkinson’s disease as an indicator of an individual patient’s future rate of progression is likely to be of modest clinical utility,” the authors write. However, targeting urate or its precursors could be a promising pathway for the development of therapies to treat Parkinson’s disease.

Glutamate- involved in blocking response to anti-epileptic medication

Mon, 14 Apr 2008 13:41:15 PST

( from http://www.rxpgnews.com ) Using a rodent model of epilepsy, researchers found one of the body’s own neurotransmitters released during seizures, glutamate, turns on a signaling pathway in the brain that increases production of a protein that could reduce medication entry into the brain. Researchers say this may explain why approximately 30 percent of patients with epilepsy do not respond to antiepileptic medications. The study, conducted by researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, and the University of Minnesota College of Pharmacy and Medical School, in collaboration with Heidrun Potschka’s laboratory at Ludwig-Maximilians-University in Munich, Germany, is available online and will appear in the May 2008, issue of Molecular Pharmacology.

“Our work identifies the mechanism by which seizures increase production of a drug transport protein in the blood brain barrier, known as P-glycoprotein, and suggests new therapeutic targets that could reduce resistance,” said David Miller, Ph.D., a principal investigator in the NIEHS Laboratory of Pharmacology and co-author on the paper.

The blood-brain barrier (BBB), which resides in brain capillaries, is a limiting factor in treatment of many central nervous system disorders. It is altered in epilepsy so that it no longer permits free passage of administered antiepileptic drugs into the brain. Miller explained that P-glycoprotein forms a functional barrier in the BBB that protects the brain by limiting access of foreign chemicals.

“The problem is that the protein does not distinguish well between neurotoxicants and therapeutic drugs, so it can often be an obstacle to the treatment of a number of diseases, including brain cancer,” Miller said. Increased levels of P-glycoprotein in the BBB has been suggested as one probable cause of drug resistance in epilepsy.

Using isolated brain capillaries from mice and rats and an animal model of epilepsy, the researchers found that glutamate, a neurotransmitter released when neurons fire during seizures, turns on a signaling pathway that activates cyclooxygenase-2 (COX-2), causing increased synthesis of P-glycoprotein in these experiments. Increased transporter expression was abolished in COX-2 knockout mice or by COX-2 inhibitors. It has yet to be shown in animals or patients that targeting COX-2 will reduce seizure frequency or increase the effectiveness of anti-epileptic drugs.

"These findings provide insight into one mechanism that underlies drug resistance in epilepsy and possibly other central nervous system disorders," said Bjoern Bauer, Ph.D., lead author on the publication. "Targeting blood-brain barrier signals that increase P-glycoprotein expression rather than the transporter itself suggests a promising way to improve the effectiveness of drugs that are used to treat epilepsy, though more research is needed before new therapies can be developed.”

Insects evolved radically different strategy to smell

Sun, 13 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Darwin's tree of life represents the path and estimates the time evolution took to get to the current diversity of life. Now, new findings suggest that this tree, an icon of evolution, may need to be redrawn. In research to be published in the April 13 advance online issue of Nature, researchers at Rockefeller University and the University of Tokyo have joined forces to reveal that insects have adopted a strategy to detect odors that is radically different from those of other organisms -- an unexpected and controversial finding that may dissolve a dominant ideology in the field.

Since 1991, researchers assumed that all vertebrates and invertebrates smell odors by using a complicated biological apparatus much like a Rube Goldberg device. For instance, someone pushing a doorbell would set off a series of elaborate, somewhat wacky, steps that culminate in the rather simple task of opening the door.

In the case of an insect's ability to smell, researchers believed that when molecules wafting in the air travel up the insect's nose, they latch onto a large protein (called a G-protein coupled odorant receptor) on the surface of the cell and set off a chain of similarly elaborate steps to open a molecular gate nearby, signaling the brain that an odor is present.

It's that way in the nematode, it's that way in mammals, it's that way in every known vertebrate, says study co-author Leslie Vosshall, head of the Laboratory of Neurogenetics and Behavior at Rockefeller University. So it's actually unreasonable to think that insects use a different strategy to detect odors. But here, we show that insects have gotten rid of all this stuff in the middle and activate the 'gate' directly.

The gate, a doughnut-shaped protein called an ion channel, provides a safe pathway for ions to flow into a cell. When molecules bind to the odor-sensitive ion channel, the protein changes its shape much like a gate or door changes its conformation as it is opened and closed. Opened, it allows millions of ions to surge into the cell. Closed, it prohibits the activity of the ions from sending a signal to the brain that an odor is present.

At the University of Tokyo, Vosshall's colleague Kazushige Touhara and his lab members puffed molecules onto cells engineered to make insect olfactory receptors. They then measured how long it took for the ion channel to open and recorded their electrical movement as they surged inside the cell via the channel. The rush of electrical activity occurred too fast for a series of steps to be involved, says Vosshall. In addition, poisoning several proteins involved in the G-protein pathway didn't affect the ions or the ion channel, suggesting that G-protein signaling isn't primarily involved in insect smell.

Experiment after experiment, the most consistent interpretation is that these are ion channels directly gated by odors, says Vosshall. But the dominant thinking in the field may have reflected an experimental bias that aimed at proving a more elaborate scheme.

The ion channels don't resemble any known ion channel on Earth, says Vosshall. They are composed of two proteins that work in tandem with one another: an olfactory receptor and its coreceptor, Or83b. While the coreceptor is common to every ion channel, the olfactory receptor is unique. Together, they form the olfactory receptor complex. Vosshall and Touhara specifically show that this complex forms nonselective cation channels, meaning that they allow any ion to pass through the gate as long as it has a positive charge.

Touhara and Vosshall developed their ion channel hypothesis in parallel with Vosshall's work on DEET, a widely used chemical in bug spray that jams the receptor complex. This research, which was published in Science last month, also showed that DEET jams other proteins that have nothing to do with smell, including several different types of ion channels that play important roles in the human nervous system. What these radically different proteins have in common, though, is that they all specifically inhibit the influx of positively charged ions into the cell. Now the curious result in the DEET paper showing that this insect repellent blocks insect olfactory receptors and unrelated ion channels makes sense, says Vosshall. I am optimistic that we can come up with blockers specific for this very strange family of insect olfactory ion channels.

Repeated methamphetamine use causes long-term adaptations in brains of mice, researchers find

Wed, 09 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Repeatedly stimulating the mouse brain with methamphetamine depresses important areas of the brain, and those changes can only be undone by re-introducing the drug, according to research at the University of Washington and other institutions. The study, which appears in the April 10 issue of the journal Neuron, provides one of the most in-depth views of the mechanisms of methamphetamine addiction, and suggests that withdrawal from the drug may not undo the changes the stimulant can cause in the brain.

The researchers set out to determine what sort of changes happen in the brain because of repeated use of the stimulant methamphetamine, and to better understand addiction-related behaviors like drug craving and relapse. Methamphetamine, also known as simply meth, is one of the most popular illegal drugs in the United States, and abuse of the drug can cause severe addiction.

Scientists have believed that abuse of drugs like meth can cause changes to the neurons in the brain and the synapses and terminals that control transmission of information in the brain. In this project, researchers focused on the mouse brain, and how it was affected by methamphetamine over 10 days, which is the mouse equivalent of chronic use in humans.

They found that the long administration and withdrawal of the drug depressed the neural terminals controlling the flow of signals between two areas of the brain, the cortex and striatum. Even a long period of withdrawal -- the equivalent of years in humans -- did not return the terminals to normal activity level. Re-introducing the drug, however, reversed the changes in the brain.

The areas affected by the drug are called pre-synaptic terminals, and are related to the flow of information from the cortex to the striatum. When a person sees something new in their environment, the scientists explained, she focuses attention on that item. At the neuron level, that process stimulates the release of dopamine, a chemical involved in transmitting signals in the brain. As the person sees the new item over and over again, the dopamine response drops, and synapses in the brain adapt to the no-longer-new item.

What happens with methamphetamine use is that the drug makes the nervous system release dopamine, which helps a user focus a lot of attention on a particular goal. Scientists believe that meth allows dopamine in the striatum to filter information coming from the cortex through the pre-synaptic terminals. The filtering of some of the terminals would help someone ignore other things and focus on that one goal or task.

After chronic use of methamphetamine, the filtering process eventually becomes a permanent depression in the activity of those terminals in the brain, the scientists found. And the only thing that can help the pre-synaptic terminals recover in mice, they found, was re-administering the drug.

What we found is that the repeated use of methamphetamine causes adaptations in the brain, and that only re-introducing the drug can reverse that, said Dr. Nigel Bamford, UW assistant professor of neurology and pediatrics and a physician at Seattle Children's Hospital. We think these changes in the brain may account for at least some of the physiological components of meth addiction.

If the mechanism turns out to be similar in people, Bamford said, this could have big effects on the treatment and management of methamphetamine addiction. One treatment for drug addiction is to give people smaller and smaller amounts of the drug to wean them from it and reduce the effects of withdrawal. Unfortunately, that method would not affect the adaptation of the neural terminals in the brain.

Now that we have some understanding of the mechanism through which meth addiction occurs, we may be able to develop other approaches to treating addiction, explained Bamford. We might be able to target some of the chemical receptors in the brain to reset the system and get rid of this depressed state in the pre-synaptic terminals.

Though scientists believe that other stimulants, like methylphenidate, may have similar effects on the brain, they caution against applying these findings to other situations. These synaptic changes may not occur in patients with underlying conditions that require treatment with stimulants, the scientists said.

Surgeons announce advance in atrial fibrillation surgery

Mon, 07 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Heart surgeons at Washington University School of Medicine in St. Louis report that by adding a simple 10-20 second step to an operative procedure they achieved a significant improvement in the outcome for the surgical treatment of atrial fibrillation (AF).

Reporting in the April issue of the Journal of Thoracic and Cardiovascular Surgery, the surgeons describe an enhancement to the Cox-Maze procedure, a surgical procedure that redirects wayward electrical impulses causing AF by creating precisely placed scars, or ablations, in the heart muscle. The Cox-Maze procedure is highly effective, offering the best long-term cure rate for persistent atrial fibrillation.

The surgeons added one ablation to the series of ablations typically made during the Cox-Maze procedure and that short step improved how well patients did after surgery. As a result, they recommend using this extra ablation in all patients undergoing the procedure.

The single additional ablation creates what we call a box lesion, explains Ralph J. Damiano Jr., M.D., the John Shoenberg Professor of Surgery at the School of Medicine. The box lesion surrounds and electrically isolates the pulmonary veins and the posterior left atrial wall from the rest of the left atrium. Our study shows excellent success when using the box lesion, and we recommend it for any patient with long-standing atrial fibrillation.

AF is the most common irregular heart rhythm and affects more than 2 million people in the United States. During atrial fibrillation, the upper chambers (atria) of the heart beat rapidly and quiver instead of contracting, drastically reducing the amount of blood they pump. AF can cause fatigue, shortness of breath, exercise intolerance, heart palpitations and stroke.

The area of the heart near the pulmonary veins is a common source of the irregular electrical impulses that can cause AF. Without the box lesion, in some patients this area could still support electrical signals that disrupt the regular contractions of the heart's upper chambers.

Led by Damiano, also chief of cardiac surgery at the School of Medicine and a cardiac surgeon at Barnes-Jewish Hospital, the Washington University surgeons revolutionized AF treatment in 2002 by helping develop a radiofrequency clamp that creates the ablation lines needed to reroute electrical impulses in the heart. The clamp directs radiofrequency energy into the heart muscle and creates a full-thickness scar.

The radiofrequency clamp procedure is quicker and easier than the original cut and sew Cox-Maze procedure, which was developed by James Cox, M.D., at Washington University in 1987. The original procedure relied on a complex series of 10 incisions in the heart muscle, creating a maze to channel errant electrical impulses where they should go. In the newer version, called Cox-Maze IV, most of these incisions were replaced by radiofrequency ablations, reducing the operation from an average of 90 minutes to about 30 minutes.

The current study involved two groups of patients with AF. One group underwent radiofrequency ablation-assisted Cox-Maze IV procedures without a box lesion and the other with a box lesion. The box lesion group had a 48 percent lower occurrence of atrial flutter and fibrillation in the first weeks after surgery. These patients also had shorter hospital stays (nine days on average) than patients who had the standard Cox-Maze IV procedure (average stay of 11 days).

Three months after surgery, 95 percent of patients who had the box lesion had no signs of AF, while only 85 percent of the patients who had the standard Cox-Maze IV procedure were free from AF. By six and 12 months postsurgery, all of the patients in the box lesion group were free from AF compared to 90 percent of the other group, although that difference was not statistically significant.

We also saw that the use of antiarrhythmic drugs was lower after three and six months in those who received a box lesion, Damiano says. These drugs can have serious side effects, and if patients can stop using them they often feel better. Overall, the use of the box lesion set was associated with shorter hospitalization, fewer medications and reduced recurrence of atrial fibrillation. We were very pleased with these results.

Compared to those without atrial fibrillation, people with the disorder are five times more likely to suffer from stroke and have up to a two-fold higher risk of death. For some patients, medications can control the abnormal heart rhythms and the risk of clotting associated with atrial fibrillation, but unlike the Cox-Maze procedure, the drugs usually do not cure the disorder.

Short and long duration sleepers gain weight

Tue, 01 Apr 2008 14:22:04 PST

( from http://www.rxpgnews.com ) Both short and long sleeping times predict an increased risk of future body weight and fat gain in adults, according to a study published in the April 1 issue of the journal SLEEP.

The study, authored by Jean-Philippe Chaput, of Laval University in Quebec, Canada, focused on 276 adults between 21-64 years of age, whose body composition measurements and self-reported sleep duration were determined. Changes in fatty indices were compared between short (five to six hours), average (seven to eight hours) and long (nine to 10 hours) duration sleeper groups.

According to the results, after adjustment for age, sex, and baseline body mass index, short duration sleepers gained 1.98 kg more and long duration sleepers gained 1.58 kg more than did average duration sleepers over six years. Short and long duration sleepers were 35 percent and 25 percent more likely to experience a 5 kg weight gain, respectively, as compared with average duration sleepers over six years. The risk of developing obesity was elevated for short and long duration sleepers as compared with average duration sleepers, with 27 percent and 21 percent increases in risk, respectively.

“Our study provides evidence that both short and long sleeping times predict an increased risk of future body weight and fat gain in adults. Furthermore, these results emphasize the need to add sleep duration to the list of environmental factors that are prevalent in our society and that contribute to weight gain and obesity. Since preventing obesity is important, a pragmatic approach adding sleep hygiene advice to encouragement towards a healthy diet and physical activity may help manage the obesity epidemic,” said Chaput.

It is recommended that adults get between seven and eight hours of nightly sleep.

The American Academy of Sleep Medicine (AASM) offers the following tips on how to get a good night’s sleep:

Follow a consistent bedtime routine.

Establish a relaxing setting at bedtime.

Get a full night’s sleep every night.

Avoid foods or drinks that contain caffeine, as well as any medicine that has a stimulant, prior to bedtime.

Do not bring your worries to bed with you.

Do not go to bed hungry, but don’t eat a big meal before bedtime either.

Avoid any rigorous exercise within six hours of your bedtime.

Make your bedroom quiet, dark and a little bit cool.

Get up at the same time every morning.

Scientists find a key culprit in stroke brain cell damage

Thu, 27 Mar 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers have identified a key player in the killing of brain cells after a stroke or a seizure. The protein asparagine endopeptidase (AEP) unleashes enzymes that break down brain cells' DNA, scientists at Emory University School of Medicine have found.

The results are published in the March 28 issue of the journal Molecular Cell.

Finding drugs that block AEP may help doctors limit permanent brain damage following strokes or seizures, says senior author Keqiang Ye, PhD, associate professor of pathology and laboratory medicine at Emory.

When a stroke obstructs blood flow to part of the brain, the lack of oxygen causes a buildup of lactic acid, the same chemical that appears in the muscles during intense exercise. In addition, a flood of chemicals that brain cells usually use to communicate with each other over-excites the cells. Epileptic seizures can have similar effects.

While some brain cells die directly because of lack of oxygen, others undergo programmed cell death, a normal developmental process where cells actively destroy their own DNA.

The mystery was: how do the acidic conditions trigger DNA damage? Ye says. This was a very surprising result because previously we had no idea that AEP was involved in this process.

AEP is a protease, a class of enzymes that cuts other proteins. AEP is also called legumain because of its relatives in plants, and is found at its highest levels in the kidney, says Ye.

He and his co-workers had suspected that another class of proteases called caspases, involved in programmed cell death, controlled DNA damage after a stroke.

At first, he and postdoctoral fellow Zhixue Liu, PhD, thought the results of a critical experiment that led them to AEP were an aberration because the experiment was performed under overly acidic conditions.

But if you can repeat the mistake, it's not a mistake, Dr. Ye says, adding that follow-up work allowed them to set aside caspases as suspects and focus on AEP.

The researchers began by looking for proteins that stick to another protein called PIKE-L, which they previously had studied because of its ability to interfere with programmed cell death in brain cells.

They discovered that PIKE-L sticks to SET, a protein that other scientists had found regulates DNA-eating enzymes involved in programmed cell death. In addition, PIKE-L appears to protect SET from attack by AEP.

Liu and Ye found that a drug scientists use to mimic the acidic overload induced by stroke activates AEP, driving it to break down DNA in brain cells. In mice genetically engineered to lack AEP, both the drug and an artificial stroke resulted in reduced DNA damage and less brain cell death than in regular mice.

This outcome suggests that AEP might be the major proteinase mediating this devastating process, the authors wrote.

Recurrence high - Cerebral aneurysm in Smokers treated by Coil Embolization

Fri, 21 Mar 2008 11:55:07 PST

( from http://www.rxpgnews.com ) Cigarette smokers who were treated for cerebral aneurysms with coil embolization (blocking of a blood vessel) are at greater risk of developing another aneurysm, say neurological surgeons at Jefferson Hospital for Neuroscience in Philadelphia in the first-known study of its kind.

In a paper published in the April issue of the Journal of Neurosurgery, researchers found there was an increased risk of recanalization (re-opening), especially in low-grade aneurysmal subarrachnoid hemorrhage (aneurysm) patients with a history of cigarette smoking, says Erol Veznedaroglu, M.D., associate professor of Neurological Surgery and director of the Division of Neurovascular Surgery and Endovascular Neurosurgery at Jefferson Medical College of Thomas Jefferson University and Thomas Jefferson University Hospital.

“To our knowledge no study documenting a correlation between aneurysm recanalization and a history of cigarette smoking history has previously been reported in the literature,” the authors say. Annually, aneurysmal subarachnoid hemorrhages are found in approximately one case per 10,000.

The study’s authors conducted a retrospective chart review of all cases involving patients admitted to their institution in 2003 for treatment of a cerebral aneurysm by coil embolization or coiling.

In coiling, a catheter is inserted into an artery in the groin, then advanced into the affected artery in the brain. The surgeon then places one or more tiny coils through the catheter into the aneurysm. The body responds by forming a blood clot around the coil, blocking off the aneurysm.

The authors searched for any correlation among the location and size of the treated aneurysm, the incidence of coil compaction, and the history of smoking as factors for recurrence. But there was no significant indication that aneurysm location and size, type of coil and packing density were causing the higher risk.

“Of the various factors that lead to a predisposition for these cerebral aneurysms, cigarette smoking is the only factor that has consistently been identified in all the populations studied, and is also the most easily preventable,” says Dr. Veznedaroglu. The quantity of cigarettes smoked was also found to have an impact on the increased risk of developing an aneurysm, he adds.

“Cigarette smoking has been directly correlated with an increased risk of intracranial aneurysm formation and growth,” the authors say. “And despite this evidence, more than one third of prior smokers continue to use nicotine after suffering an aneurysm, especially patients who started smoking at a young age and those with a history of depression or alcohol abuse.”

However in the group of patient cases reviewed, the authors did not find a significant trend between smoking cessation after aneurysm treatment and the incidence of aneurysm recurrence, but the sample size was not large enough to demonstrate statistical significance.

“Nevertheless, patients with known cerebral aneurysms should be aggressively counseled about the risk of cigarette smoking,” Dr. Veznedaroglu says.

Second depth-perception method in brain

Mon, 17 Mar 2008 05:01:17 PST

( from http://www.rxpgnews.com ) It’s common knowledge that humans and other animals are able to visually judge depth because we have two eyes and the brain compares the images from each. But we can also judge depth with only one eye, and scientists have been searching for how the brain accomplishes that feat.

Now, a team led by a scientist at the University of Rochester believes it has discovered the answer in a small part of the brain that processes both the image from a single eye and also with the motion of our bodies.

The team of researchers, led by Greg DeAngelis, professor in the Department of Brain and Cognitive Sciences at the University of Rochester, has published the findings in the March 20 online issue of the journal Nature.

“It looks as though in this area of the brain, the neurons are combining visual cues and non-visual cues to come up with a unique way to determine depth,” says DeAngelis.

DeAngelis says that means the brain uses a whole array of methods to gauge depth. In addition to two-eyed “binocular disparity,” the brain has neurons that specifically measure our motion, perspective, and how objects pass in front of or behind each other to create an approximation of the three-dimensional world in our minds.

The researchers say the findings may help instruct children who were born with misalignment of the eyes to restore more normal functions of binocular vision in the brain. The discovery could also help construct more compelling virtual reality environments someday, says DeAngelis, since we have to know exactly how our brains construct three-dimensional perception to make virtual reality as convincing as possible.

The neural mechanism is based on the fact that objects at different distances move across our vision at different speeds due to a phenomenon called motion parallax, says DeAngelis. When staring at a fixed object, any motion we make will cause things nearer than the object to appear to move in the opposite direction, and more distant things to appear to move in the same direction.

To figure out the real three-dimensional layout of what it sees, DeAngelis says the brain needs one more piece of information and it pulls in this information from the motion of the eyeball itself.

According to DeAngelis, the neurons in the middle temporal area of the brain are combining visual information and physical movement to extract depth information. As the dragon illusion demonstrates, the motion of near and far objects can be confused. But if the eye is moving while tracking the overall movement of the group of objects, it gives the middle temporal neurons enough information to grasp that the object moving fastest in the same direction must be the closest object, and the one moving slowest must be the farthest, says DeAngelis.

“We use binocular disparity, occlusion, perspective, and our own motion all together to create a representation of the real, 3D world in our minds,” says DeAngelis.

WHI follow-up study: Risks of long-term hormone therapy continue to outweigh benefits

Tue, 04 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) New results from the Women's Health Initiative (WHI) confirm that the health risks of long-term use of combination (estrogen plus progestin) hormone therapy in healthy, postmenopausal women persist even a few years after stopping the drugs and clearly outweigh the benefits. Researchers report that about three years after women stopped taking combination hormone therapy, many of the health effects of hormones such as increased risk of heart disease are diminished, but overall risks, including risks of stroke, blood clots, and cancer, remain high. The WHI is sponsored by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

Results of the WHI three-year follow-up study of the estrogen-plus-progestin clinical trial are published in the March 5, 2008, issue of the Journal of the American Medical Association.

The good news is that after women stop taking combination hormone therapy, their risk of heart disease appears to decrease, noted Elizabeth G. Nabel, M.D., NHLBI director. However, these findings also indicate that women who take estrogen plus progestin continue to be at increased risk of breast cancer, even years after stopping therapy. Today's report confirms the study's primary conclusion that combination hormone therapy should not be used to prevent disease in healthy, postmenopausal women.

The FDA recommends that hormone therapy never be used to prevent heart disease, and, when hormone therapy is used for menopausal symptoms, it should only be taken at the smallest dose and for the shortest time possible.

The new findings are from a follow-up study of 15,730 postmenopausal women with an intact uterus, ages 50 to 79 years (average age of 63) at enrollment, who participated in the WHI estrogen-plus-progestin clinical trial. Participants were randomly assigned to receive a combination of estrogen (0.625 milligrams of conjugated equine estrogens per day) plus progestin (2.5 mg of medroxyprogesterone acetate) or placebo (inactive pill). The main estrogen-plus-progestin study was stopped in 2002 after an average of 5.6 years of treatment due to an increase in breast cancer. Women on combination hormone therapy were also at increased risk of stroke, blood clots, and heart disease, while their risk of colorectal cancer and hip fractures was lower, compared to women who did not take hormone therapy.

The follow-up study began in July 2002 after women in the study were instructed to stop taking combination hormone therapy, and continued through March 2005, with participants followed for an average of 2.4 years. All study participants were examined at least once a year by a WHI clinician and received an annual breast examination and mammogram, with biopsies performed as needed. During the follow-up study, the numbers of heart attacks, strokes, and blood clots were not significantly different between the two groups (overall, 343 cardiovascular events among those who initially received hormone therapy versus 323 among those who did not). In addition, the number of deaths was not significantly different (233 women who had been in the hormone therapy group died, versus 196 women who had been in the placebo group).

Reduction of stroke risk with aerobic fitness

Fri, 22 Feb 2008 06:27:06 PST

( from http://www.rxpgnews.com ) A moderate level of aerobic fitness can significantly reduce stroke risk for men and women, according to a large, long-running study presented at the American Stroke Association’s International Stroke Conference 2008.

“Fitness has a protective effect regardless of the presence or absence of other stroke risk factors, including family history of cardiovascular disease, diabetes, high blood pressure, elevated cholesterol levels and high body mass index,” said Steven Hooker, Ph.D., the study’s lead author.

“This study is the first to suggest that there may be a significant independent association between cardiorespiratory fitness (CRF) and fatal and nonfatal stroke in men and nonfatal stroke in women,” said Hooker, director of the Prevention Research Center at the University of South Carolina Arnold School of Public Health, Columbia, S.C.

About 780,000 U.S. adults suffer a stroke each year, and stroke is a leading cause of serious, long-term disability in the United States, according to the American Stroke Association. It’s often fatal, claiming about 150,000 lives and ranking as the No. 3 cause of death. Researchers analyzed data on more than 60,000 people — 46,405 men and 15,282 women who participated in the Aerobics Center Longitudinal Study between 1970 and 2001 at the Cooper Aerobics Center in Dallas. The participants, ages 18 to 100 and free of known cardiovascular disease when they entered the study, were followed for an average of 18 years. During that time, 863 people — 692 men and 171 women — had strokes.

Upon entering the study, each participant took a test to measure CRF in which they walked on a treadmill at increasing grade and/or speed until they reached their maximal aerobic capacity.

Although many previous studies have looked at an association between self-reported physical activities and cardiovascular disease, few have used direct measurements such as the CRF measure used in this study, Hooker said. This is also the first study to explore the association between CRF and risk of stroke in women.

Men in the top quartile (25 percent) of CRF level had a 40 percent lower relative risk of stroke compared to men in the lowest quartile. That inverse relationship remained after adjusting for other factors such as smoking, alcohol intake, family history of cardiovascular disease, body mass index (an estimation of body fatness), high blood pressure, diabetes and high cholesterol levels, he said.

Among women, those in the higher CRF level had a 43 percent lower relative risk than those in the lowest fitness level.

The overall stroke risk dropped substantially at the moderate CRF level, with the protective effect persisting nearly unchanged through higher fitness levels. That corresponds to 30 minutes or more of brisk walking, or an equivalent aerobic activity, five days a week.

“We found that a low-to-moderate amount of aerobic fitness for men and women across the whole adult age spectrum would be enough to substantially reduce stroke risk,” Hooker said.

“Although stroke death rates have declined over the past few decades, the public health burden of stroke-related disabilities continues to be large and may even increase in coming years, as the population ages.”

Physical activity is a major modifiable cardiovascular disease risk factor. Increasing the nation’s CRF through regular physical activity could be a vital weapon to lower the incidence of stroke in men and women, he said.

One of the study’s limitations is that most of the participants were white, well-educated and middle-upper income, he said. He recommended that data be collected from other populations.

Cocaine's effects on brain metabolism may contribute to abuse

Mon, 18 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) UPTON, NY - Many studies on cocaine addiction - and attempts to block its addictiveness - have focused on dopamine transporters, proteins that reabsorb the brain's reward chemical once its signal is sent. Since cocaine blocks dopamine transporters from doing their recycling job, it leaves the feel-good chemical around to keep sending the pleasure signal. Now a new study conducted at the U.S. Department of Energy's Brookhaven National Laboratory suggests that cocaine's effects go beyond the dopamine system. In the study, cocaine had significant effects on brain metabolism, even in mice that lack the gene for dopamine transporters.

In dopamine-transporter-deficient mice, these effects on metabolism are clearly independent of cocaine's effects on dopamine, said Brookhaven neuroscientist Panayotis (Peter) Thanos, who led the research. These metabolic factors may be a strong regulator of cocaine use and abuse, and may also suggest new avenues for addiction treatments. The study will appear in the May 2008 issue of the journal Synapse, and will be available online on Monday, February 18, 2008.

The scientists used positron emission tomography, or PET scanning, to measure brain metabolism in dopamine-transporter deficient mice (known as DAT knockouts) and in littermates that had normal dopamine transporter levels. In this technique, the scientists administer a radioactively labeled form of sugar (glucose) - the brain's main fuel - and use the PET scanner to track its site-specific concentrations in various brain regions. They tested the mice before and after cocaine administration, and compared the results to mice treated with saline instead of the drug.

Before any treatment, mice lacking dopamine transporters had significantly higher metabolism in the thalamus and cerebellum compared with normal mice. This elevated metabolism may be linked to chronically high levels of dopamine in the DAT knockout mice. It also suggests that dopamine levels may play an important role in modulating glucose levels in these brain areas, which play important roles integrating sensory information, learning, and motor function.

Interestingly, DAT knockout mice have been suggested as an animal model for attention-deficit hyperactivity disorder (ADHD). Elevated metabolism due to persistent elevated dopamine levels may be a factor contributing to the symptoms of ADHD, Thanos said.

After the scientists administered cocaine, whole brain metabolism decreased in both groups of mice, but more significantly in normal mice than in DAT knockouts. The scientists were able to detect this reduction in metabolism in a wide range of brain regions in the normal mice, suggesting that these decreases in metabolism are somehow associated with the blockade of dopamine transporters by cocaine.

The scientists also observed a reduction in metabolism in the thalamus region in the DAT knockout mice. This effect may likely be due to the effect of cocaine on other neurotransmitter systems, for example, norepinepherine or serotonin.

In summary, cocaine exposure has an effect on regional brain activity, which is mostly driven by dopamine action and to a secondary degree norepinephrine or serotonin. These results also support the idea that the thalamus and the cerebellum play key roles in cocaine's mechanism of effect on sensory input, learning, and motor function. This is particularly of interest in better understanding the mechanism of cocaine addiction as well as the neurobiology of ADHD.

Research shows a daily dose of beetroot juice can beat high blood pressure

Wed, 06 Feb 2008 05:39:37 PST

( from http://www.rxpgnews.com ) Researchers at Barts and The London School of Medicine have discovered that drinking just 500ml of beetroot juice a day can significantly reduce blood pressure. The study, published online today in the American Heart Association journal Hypertension, could have major implications for the treatment of cardiovascular disease.

Lead by Professor Amrita Ahluwalia of the William Harvey Research Institute at Barts and The London School of Medicine, and Professor Ben Benjamin of Peninsula Medical School, the research reveals that it is the ingestion of dietary nitrate contained within beetroot juice - and similarly in green, leafy vegetables - which results ultimately in decreased blood pressure. Previously the protective effects of vegetable-rich diets had been attributed to their antioxidant vitamin content.

Professor Ahluwalia and her team found that in healthy volunteers blood pressure was reduced within just 1 hour of ingesting beetroot juice, with a peak drop occurring 3-4 hours after ingestion. Some degree of reduction continued to be observed until up to 24 hours after ingestion. Researchers showed that the decrease in blood pressure was due to the chemical formation of nitrite from the dietary nitrate in the juice. The nitrate in the juice is converted in saliva, by bacteria on the tongue, into nitrite. This nitrite-containing saliva is swallowed, and in the acidic environment of the stomach is either converted into nitric oxide or re-enters the circulation as nitrite. The peak time of reduction in blood pressure correlated with the appearance and peak levels of nitrite in the circulation, an effect that was absent in a second group of volunteers who refrained from swallowing their saliva during, and for 3 hours following, beetroot ingestion.

New devices to boost nematode research on neurons and drugs

Tue, 05 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) A pair of new thin, transparent devices, constructed with soft lithography, should boost research in which nematodes are studied to explore brain-behavior connections and to screen new pharmaceuticals for potential treatment of parasitic infections in humans, report 10 scientists at three institutions.

The tools -- an artificial soil device and a waveform sampler device, both of which can be held easily in a human hand -- are detailed in a paper appearing online ahead of regular publication by the Journal of Neurophysiology.

The devices take advantage of a microfluidic fabrication technique, which allows for the presence of channels, chambers or ports, for gas permeability and transparency and for using fluids to deliver stimuli with precision. The major improvement over previous tools is that these new ones are agarose-free, using micron-scale channels and pillars that mimic real soil particles.

The newly reported devices provide a near natural environment for soil-dwelling roundworms (Caenorhabditis elegans, or C. elegans) that measure barely a millimeter in length. The nematodes move normally, but slightly compressed so that highly sensitive microscopes can be used to monitor individual fluorescent-injected neurons in real time during experiments.

There is a commonality between these devices that is really going to help us understand how the nervous system works, said lead researcher Shawn Lockery, a professor of biology and member of the Institute of Neuroscience at the University of Oregon.

The artificial soil device consists of a hexagonal array of microscopic pillars sandwiched between a glass cover slip and a bulk material from which the pillars protrude, Lockery said. The worm wanders around in a one-centimeter square area as a river of mostly water flows through it. We can change the solution the nematode is exposed to in ways that are relevant to the research that is being conducted.

For instance, researchers can manipulate the levels of sodium chloride and oxygen in the water being injected into the devices.

As a proof of principle, researchers had to show that the behavior of the nematodes is essentially normal in the new devices, meaning that the worms crawl like they do on an agar surface. But nematodes don't live on exposed agar surfaces in real life, Lockery said. Instead, they are found within soil and easily collected in the wild in rotting fruit.

The beauty of this system is that it reproduces standard laboratory behavior, but it does so in a context that is probably more normal in terms of the worms' real-life environment, he said. You get forward and reverse locomotion, and the nematodes also do the omega turn, in which a worm's head bends around to touch the tail during forward locomotion, forming a shape like the Greek omega.

The waveform device features 18 different channels, with each divided into domains with unique amplitudes and wavelengths to manipulate how a nematode moves. Instead of using posts to mimic real soil, depressions or channels provide natural areas -- even some that don't occur in nature -- for the nematodes to crawl through. This ability to change the channels but still allow the worms to move about proved the principle in this case, Lockery said. What we found from this is that these animals are remarkably adaptable to a wide range of situations.

The artificial soil device, Lockery said, will help to study how brains generally process sensory information and for high-through-put screening of new drugs for their biological effects. Such research, he said, could lead to new treatments for some two billion people infected annually by parasitic nematodes, as well as new tools to reduce nematode-caused losses in world agriculture.

The waveform device could enhance research on brain-behavior connections. C-elegans have only 302 neurons, compared to 100 billion neurons in the human brain, Lockery said. At least 50 percent of the proteins in the nematode brain are identical to those in human brains. C. elegans is the only animal for which we have a complete anatomical reconstruction of the nervous system -- a complete wiring diagram of the brain. This greatly accelerates analyses of brain function in this organism, he said.

Gene protects adults abused as children from depression

Mon, 04 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Some forms of a gene that controls the body's response to stress hormones appear to protect adults who were abused in childhood from depression, psychiatrists have found.

People who had been abused as children and who carried the most protective forms of the gene, called corticotropin-releasing hormone receptor one (CRHR1), had markedly lower measures of depression, compared with people with less protective forms, the researchers found in a recent study.

The findings could guide doctors in finding new ways to treat depression in people who were abused as children, says senior author Kerry Ressler, MD, PhD, assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine.

We know that childhood abuse and early life stress are among the strongest contributors to adult depression, and this study again brings to light the importance of preventing them, Dr. Ressler says. But when these tragic events do occur, studies like this one ultimately can help us learn how we might be able to better intervene against the pathology that often follows.

The results of the study, performed on two separate racially and economically distinct groups from the Atlanta area, were published in the February 4 issue of the Archives of General Psychiatry.

The first and second authors of the study are Rebekah Bradley, PhD, at the Atlanta Veterans Affairs Medical Center and Elisabeth Binder, MD, PhD, at Emory University and the Max Planck Institute for Psychiatry in Munich, Germany. Dr. Ressler, who also is a scientist at Emory's Yerkes National Primate Research Center and a member of the Center for Behavioral Neuroscience, and Joseph Cubells, MD, PhD, associate professor of human genetics at Emory University School of Medicine, are co-senior authors.

The team's research illustrates how life events and genetic influences can combine in complex ways, leading to depression or protection from it. Almost 15 million U.S. adults have major depression, according to the National Institute of Mental Health.

The study also supports previous evidence that corticotropin-releasing hormone (CRH) and related hormones play a role in depression. Other studies have found increased levels of CRH and altered levels of its receptor in the brains of patients with depression.

Some pharmaceutical firms are testing compounds that block CRHR1 as potential medications for depression.

The receptor for a hormone acts like a receiver or radar dish for messages sent between cells. CRH stimulates the pituitary gland to release another hormone, adrenocorticotropin, which in turn induces the release of cortisol from the adrenal cortex.

Extreme stress in childhood can over-activate this cascade of hormones, increasing the risk of depression in adulthood, Dr. Ressler says.

Our results suggest that genetic differences in signals mediated by CRH may amplify or soften the developmental effects that childhood abuse can have -- effects that can raise the risk of depression in adults, he says.

In the study, scientists began by interviewing more than 470 adults and testing their DNA, looking for alternative spellings or SNPs (single nucleotide polymorphisms) in several parts of the CRHR1 gene.

This first group was mostly black and a majority had a monthly income less than $1,000. The researchers measured their symptoms of depression and had them answer questionnaires about childhood trauma. Their responses were categorized as low, mild, moderate and severe.

Overall, people with a history of moderate or severe child abuse had depression symptoms that averaged about double the level of those with low or mild child abuse scores.

Roughly 30 percent of the group had variations in the CRHR1 gene that together appeared to be protective if moderate to severe abuse had occurred. People who had inherited two copies of the most protective forms of the gene, or haplotypes, had average depression symptoms that were about half those of people who had not inherited those haplotypes. A haplotype comprises several SNPs that frequently appear together.

These differences in depression symptoms were only seen in people with histories of moderate to severe abuse; depression levels were not significantly different in people with low to mild abuse.

The most significant SNPs appear in the part of the gene preceding the region that encodes the receptor protein, suggesting that the variations may affect its regulation rather than the composition of the protein, the authors say.

The findings were strengthened when the researchers repeated the study in 199 white, middle-income adults and came up with similar results, suggesting that the genetic variations act in a way that is independent of ethnic background or economic status.

Naked mole-rats bear chili pepper heat

Mon, 28 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Pity the tiny naked mole-rat. The buck-toothed, sausage-like rodent lives by the hundreds in packed, oxygen-starved burrows some six feet under ground. It is even cold-blooded -- which, as far as we know, is unique among mammals.

You can feel their pain. But, they can't feel ours.

Evolution has benefited naked mole-rats by ridding them of a body chemical called Substance P, a neurotransmitter released by pain fibers that send signals to the central nervous system in mammals after making contact with things that cause long-lasting, achy pain.

A better understanding of how Substance P works in the strange rodents may lead to new analgesic drugs for people with chronic pain who do not respond well to current medication, according to Thomas Park, associate professor of biological sciences at the University of Illinois at Chicago, and Gary Lewin of the Max-Delbrück Center for Molecular Medicine in Berlin, principal authors of a study appearing Jan. 29 in the free-access journal PLoS Biology.

Park, Lewin and their laboratory teams in Chicago and Berlin used a modified herpes cold sore virus to carry genes for Substance P to the rodents' nerve fibers.

We were able to rescue their ability to feel pain, said Park. His research group restored Substance P and the naked mole-rats' ability to sense the burning sensation other mammals feel when subjected to capsaicin, the active ingredient in chili peppers.

The restored sensitivity was limited to just one rear foot of each tested rodent. They'd pull their foot back and lick it, in response to the stimulus, said Park. Other feet were impervious to the sting of capsaicin.

Capsaicin is very specific for exciting the fibers that normally have Substance P, said Park. They're not the fibers that respond to a pin prick or pinch, but the ones that respond after an injury or burn and produce longer-lasting pain.

But the researchers found that mole-rats remained completely insensitive to acids, indicating a fundamental difference in how their nerves respond to this stimulus.

Acid acts on the capsaicin receptor and on another family of receptors called acid-sensitive ion channels, Park said. Acid is not as specific as capsaicin. The mole-rat is the only animal that shows completely no response to acid.

Park said the research adds to knowledge about the neurotransmitter Substance P.

This is important specifically to the long-term, secondary-order inflammatory pain. It's the pain that can last for hours or days when you pull a muscle or have a surgical procedure, he said.

Park said naked mole-rats provide a new model system that is different from all other animals he has studied.

We're learning which nerve fibers are important for which kinds of pain, so we'll be able to develop new strategies and targets.

Naked mole-rats, native to east-central Africa, developed a protective reaction to acids through evolution. Living in tight underground quarters, the mole-rats exhale high levels of carbon dioxide, which becomes acid when it touches skin and mucous tissue in the nose, eyes and mouth. But the mole-rats have evolved to become desensitized to the stinging pain of acid.

The UIC biologist plans to study other animals, both closely related and unrelated -- such as Alaskan marmots that burrow in high CO2 environments -- to examine how they have evolved similar strategies to cope with acid-rich living conditions.

Human brain has impressive auditory memory

Sun, 20 Jan 2008 10:09:46 PST

( from http://www.rxpgnews.com ) The human brain is capable of detecting the slightest visual and auditory changes. Whether it is the flash of a student’s hand into the air or the faintest miscue of a flutist, the brain instantaneously and effortlessly perceives changes in our environment. Several studies have indicated, however, that even a small span of time in between pre- and post-change images can disturb the brain’s ability to detect visual discrepancies.

“The pre-change scene must be memorized in some way,” explained psychologists Laurent Demany, Wiebke Trost, Maja Serman and Catherine Semal from the University of Bordeaux and the French National Center for Scientific Research (CNRS). “In the visual domain, numerous experiments have shown that even a very short gap of less than 100ms can dramatically disrupt our ability to detect a local change in complex images. Following such a gap, local changes can be detected only in very simple images.” This phenomenon is known as ‘change blindness.’

In a recent study, the aforementioned psychologists assessed the effect of time gaps on change detection in audition. Their goal was to determine if the brain uses similar mechanisms to perceive auditory changes as it does with vision. Participants had to detect a pitch change in one tone presented together with other tones. The complexity of the pre-change sound was varied, as well as the duration of the silent interval between the pre- and post-change sounds.

The experimenters reasoned that if auditory change detection is similar to the visual process, a complex sound (including many tones) should be remembered less well than a simple sound (including few tones). The psychologists discovered, however, that this was not the case. The participants were able to remember even the most complex sounds -- reaching up to 12 tones -- despite the time delays.

The results of the study, which appear in the January 2008 issue of Psychological Science, a journal of the Association for Psychological Science, indicate that the brain uses more efficient mechanisms in auditory memory than in visual memory. To that extent, the human brain appears to be a keener detective of auditory change than visual change.

Weill Cornell team discovers how brain's own tPA helps regulate blood flow to neurons

Thu, 17 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (Jan. 17, 2008) -- The human brain contains its own store of a powerful enzyme (and stroke drug) called tissue plasminogen activator (tPA), which appears to be a key regulator of blood flow to brain cells, a team at the Weill Cornell Medical College in New York City reports.

We found that this natural tPA boosts blood flow to brain cells via its influence on nitric oxide synthase, which is essential to the production of nitric oxide (NO). NO is a well-known vasodilator -- a drug or chemical that widens blood vessels -- so, more NO means better blood flow to neurons as they become more active, explains study senior author Dr. Costantino Iadecola, the George C. Cotzias Distinguished Professor of Neurology and Neuroscience at Weill Cornell Medical College, and chief of the Division of Neurobiology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The findings have just been published in this week's online issue of Proceedings of the National Academies of Science.

Besides elucidating the role of naturally produced tPA in neuronal blood flow, the new findings could have implications for the study of stroke and Alzheimer's disease. Both conditions are associated with marked declines in natural brain levels of tPA.

TPA has become a star of sorts in cardiovascular research over the past two decades, ever since scientists discovered its remarkable ability to break up clots.

Essentially, tPA, a powerful protease enzyme, cleaves a protein called plasminogen into plasmin, an enzyme that quickly 'eats up' clots, notes study lead author Dr. Laibaik Park, instructor in neuroscience at Weill Cornell. For that reason, doctors often administer a shot of tPA to stroke patients within minutes or hours of an attack.

But other research had also detected tPA occurring naturally in the human brain, with levels of the enzyme rising as brain cell activity increased.

What really piqued our interest was the finding from recent studies that tPA somehow modulates the activity of a protein lying on the surface of neurons called the NMDA receptor, Dr. Iadecola explains. This receptor serves as a gateway of communication between adjoining neurons, with glutamate being the 'currency' of exchange. Fluctuating levels of tPA seemed to influence just how much of that currency got through as brain cells became more or less active.

Exploring this mechanism further, Dr. Iadecola's team utilized a genetically engineered knockout mouse that lacked neuronal tPA. They tweaked the mouse's whiskers and watched blood flow in the area of the rodent's brain linked to whisker sensitivity.

In the knockout mouse, blood flow in that area did not change as much upon whisker stimulation -- confirming that tPA is necessary to boosting local blood flow, Dr. Iadecola says.

But how was tPA working, exactly? The prevailing theory -- that the enzyme impacted directly on the NMDA receptor -- was quickly proven wrong. We found that tPA was not acting as any kind of direct 'choke' on the NMDA receptor to allow more or less glutamate into the cell, says Eduardo Gallo, a graduate student in the Department of Neurology and Neuroscience, who played a key role in the study.

So, the team looked elsewhere at other rate-limiting mechanisms that might explain tPA's effects.

One of the end-products of NMDA receptor activity is nitric oxide (NO), a powerful vasodilator, Gallo notes. In our experiments, we discovered that tPA helps control how much NO can be made by activation of the NMDA receptor. TPA does so by boosting the ability of neuronal nitric oxide synthase (nNOS) -- an enzyme -- to produce NO. More tPA means more active nitric oxide synthase -- and more of this enzyme means more vessel-widening NO. The end result: a localized boost in blood flow to brain cells.

Questions remain, however. TPA exists outside the brain cell, but the nNOS activity and NO production goes on inside the neuron, Dr. Iadecola points out. That means there's some kind of biochemical chain connecting external tPA to these internal mechanisms, he says. Identifying the key players in that pathway will be a key part of our research going forward.

The new discoveries will have exciting implications for brain research, he says.

More and more, we are realizing that alterations in the availability of blood to brain cells is crucial to stroke and post-stroke recovery, and in the debilitating loss of neuronal function that underlies Alzheimer's disease and other dementias, Dr. Iadecola says.

It is possible that drugs or other interventions that manipulate the brain's natural supply of tPA could help preserve neurological function after stroke or Alzheimer's, or even help reverse some of the damage, he says. Those types of treatments are still a long way off, but our new understanding how tPA works to keep neurons healthy and active is a crucial first step in that research.

Carotid artery stenting- questions still remain

Wed, 16 Jan 2008 13:34:29 PST

( from http://www.rxpgnews.com ) A procedure called carotid artery stenting (CAS) has emerged as a minimally invasive alternative to surgery, called carotid endarterectomy (CEA), for patients with dangerous narrowing of the arteries supplying blood to the brain. However, questions remain about the best uses of this procedure—especially whether it is an appropriate alternative to surgery for "low-risk" patients, according to a special article in the January/February issue of Annals of Vascular Surgery.

"Currently, the choice of CEA versus CAS in individual patients is based more on individual practitioner experience than on clear evidence-derived guidelines," according to the new article by Drs. Philip P. Goodney and Richard J. Powell of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. "Nonetheless, the popularity of less-invasive therapy combined with marketing of new CAS systems has increased the utilization of CAS."

Drs. Goodney and Powell review and summarize the research evidence on CAS to prevent stroke in patients with narrowing (stenosis) of the carotid arteries. In the CAS procedure, an expandable mesh device called a stent is placed to increase blood flow through the area of stenosis.

Recently, several randomized controlled trials—the strongest category of scientific evidence—have directly compared the results of CAS and CEA. It has now been fairly well established that CAS and CEA yield comparable results in "high-risk" patients.

However, debate continues as to the role of CAS in the much larger group of "low-risk" patients. Some studies suggest that CAS and CEA produce similar results, but others have found a lower rate of serious complications and death in patients undergoing surgery.

Drs. Goodney and Powell note several limitations of the research that make it difficult to compare results between trials. Studies being conducted now will help to clarify the relative performance of the two techniques in both high-risk and low-risk patients. A key question will be whether CAS or CEA is the better choice for patients considered high-risk because of medical conditions.

Other issues that will need to be worked through include refinements in the design of CAS systems and the role of detailed imaging studies in guiding treatment decisions. "Ongoing randomized trials will help determine optimal revascularization strategies in the future," the authors conclude.

Overweight people may not know when they've had enough

Wed, 09 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) UPTON, NY - Researchers at the U.S. Department of Energy's Brookhaven National Laboratory have found new clues to why some people overeat and gain weight while others don't. Examining how the human brain responds to satiety messages delivered when the stomach is in various stages of fullness, the scientists have identified brain circuits that motivate the desire to overeat. Treatments that target these circuits may prove useful in controlling chronic overeating, according to the authors. The study is published online and will appear in the February 15, 2008 issue of NeuroImage.

By simulating feelings of fullness with an expandable balloon we saw the activation of different areas of the brain in normal weight and overweight people, said lead author Gene-Jack Wang of Brookhaven Lab's Center for Translational Neuroimaging. The overweight subjects had less activation in parts of the brain that signal satiety in normal weight subjects. The overweight subjects were also less likely than normal weight subjects to report satiety when their stomachs were moderately full. These findings provide new evidence for why some people will continue to eat despite having eaten a moderate-size meal, said Wang.

Wang and colleagues studied the brain metabolism of 18 individuals with body mass indices (BMI) ranging from 20 (low/normal weight) to 29 (extremely overweight/borderline obese). Each study participant swallowed a balloon, which was then filled with water, emptied, and refilled again at volumes that varied between 50 and 70 percent. During this process, the researchers used functional magnetic resonance imaging (fMRI) to scan the subjects' brains. Subjects were also asked throughout the study to describe their feelings of fullness. The higher their BMI, the lower their likelihood of saying they felt full when the balloon was inflated 70 percent.

One notable region of the brain - the left posterior amygdala - was activated less in the high-BMI subjects, while it was activated more in their thinner counterparts. This activation was turned on when study subjects reported feeling full. Subjects who had the highest scores on self-reports of hunger had the least activation in the left posterior amygdala.

This study provides the first evidence of the connection of the left amygdala and feelings of hunger during stomach fullness, demonstrating that activation of this brain region suppresses hunger, said Wang. Our findings indicate a potential direction for treatment strategies - be they behavioral, medical or surgical -- targeting this brain region.

The scientists also looked at a range of hormones that regulate the digestive system, to see whether they played a role in responding to feelings of fullness. Ghrelin, a hormone known to stimulate the appetite and cause short-term satiety, showed the most relevance. Researchers found that individuals who had greater increases in ghrelin levels after their stomachs were moderately full also had greater activation of the left amygdala. This indicates that ghrelin may control the reaction of the amygdala to satiety signals sent by the stomach, said Wang.

This study was funded by the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science, the National Institute on Drug Abuse (NIDA), the National Institute of Diabetes and Digestive and Kidney Diseases, the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the General Clinical Research Center at University Hospital Stony Brook. DOE has a long-standing interest in research on brain chemistry gained through brain-imaging studies. Brain-imaging techniques such as MRI are a direct outgrowth of DOE's support of basic physics and chemistry research.

The current study is part of a major focus of research at Brookhaven Lab on the neurobiology of eating disorders and obesity and their treatment. Earlier studies at the Lab have:

Cognitive, genetic clues identified in imaging study of alcohol addiction

Tue, 25 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) People with clinical addictions know first-hand the ravages the disease can take on almost every aspect of their lives. So why do they continue addictive behaviors, even after a period of peaceable abstinence

Some answers appear rooted in regions of the brain active during decision making.

It's perhaps not just that people are slaves to pleasure, but that they have trouble thinking through a decision, said Charlotte Boettiger, an assistant professor of psychology at the University of North Carolina at Chapel Hill, and lead author of a study in the December issue of the Journal of Neuroscience that took a novel tack in addiction imaging research.

Our data suggest there may be a cognitive difference in people with addictions, Boettiger said. Their brains may not fully process the long-term consequences of their choices. They may compute information less efficiently.

The study also found that a variant of the COMT gene, which controls the level of the neurotransmitter dopamine in the cortex, was associated with a tendency to make impulsive decisions and with high activity in certain brain areas during decision making.

Current medications for addictions are not universally effective; many either mimic the addictive substance to help people get through withdrawal periods or block the substance to prevent its effects. For stimulants, such as methamphetamines, there are no therapies yet, Boettiger said.

What's exciting about this study is that it suggests a new approach to therapy. We might prescribe medications, such as those used to treat Parkinson's or early Alzheimer's disease, or tailor cognitive therapy to improve executive function, said Boettiger, who led the study as scientist at the University of California, San Francisco's Gallo Clinic and Research Center.

I am very excited about these results because of their clinical implications, said Dr. Howard Fields, a professor of neurology at UCSF and an investigator in the Gallo Center.

The genetic findings raise the hopeful possibility that treatments aimed at raising dopamine levels could be effective treatments for some individuals with addictive disorders, said Fields, who is senior author of the study.

Most addiction imaging studies have focused on the brain response to drug-related stimuli.

Boettiger used functional magnetic resonance imaging (fMRI), which shows brain activity while a subject performs a function, to see what happened inside their heads when sober alcoholics and people in a non-alcoholic control group made decisions between immediate and delayed rewards.

Boettiger recruited 24 subjects; 19 provided fMRI data, nine were recovering alcoholics in abstinence and 10 had no history of substance abuse. Another five were included in the genotyping analysis.

At the fMRI research facility at the University of California, Berkeley, the subjects were asked to decide between receiving a small monetary award immediately or wait for a larger payoff. The scenarios were hypothetical, but the tasks measured rational thinking and impulsivity; sober alcoholics chose the now reward almost three times more often than the control group, reflecting more impulsive behavior.

While decisions were being made the imaging detected activity the predicted individual choice in regions associated with decision making -- the posterior parietal cortex, the dorsal prefrontal cortex, the anterior temporal lobe and the orbital frontal cortex.

People who sustain damage to the orbital frontal cortex generally suffer impaired judgment; they manage money poorly and act impulsively. Boettiger's study revealed reduced activity in the orbital frontal cortex in the brains of subjects who preferred nowover later, most of whom had a history of alcoholism.

The orbital frontal cortex activity may be a neural equivalent of long-term consequences. Think of the orbital frontal cortex as the brakes, Boettiger said. With the brakes on, people choose for the future; without the brakes they choose for the short-term gain.

The dorsal prefrontal cortex and the parietal cortex often form cooperative circuits, and this study found that high activity in both is associated with a bias toward choosing immediate rewards.

The frontal and parietal cortex are also involved in working memory -- being able to hold data in mind over a short delay. When asked to choose between $18 now or $20 in a month, the subjects had to calculate how much that $18 (or what it could buy now) would be worth in a month and then compare it to $20 and decide whether it would be worth the wait.

The parietal cortex and the dorsal prefrontal cortex were much more active in people unwilling to wait. This could mean, Boettiger said, that the area is working less efficiently in those people.

The COMT gene has two common variants with a single amino acid difference at position 158; valine (Val) or methionine. The Val form of the gene is associated with lower dopamine levels, and Boettiger's study showed that people with two copies of the Val allele (resulting in the lowest dopamine levels) had significantly higher frontal and parietal activity and chose now over later significantly more often.

We have a lot to learn, Boettiger said. But the data take a significant step toward being able to identify subtypes of alcoholics, which could help tailor treatments, and may people who are at risk for developing addictions and provide earlier intervention.

The bigger picture, Boettiger said, is that her study provides more evidence that addiction is a disease, something even some of her peers do not yet believe.

It's not unlike chronic diseases, such as diabetes, she said. There are underlying genetic and other biological factors, but the disease is triggered by the choices people make.

It wasn't that long ago that we believed schizophrenia was caused by bad mothers and depression wasn't a disease. Hopefully, in 10 years, we'll look back and it will seem silly that we didn't think addiction was a disease, too.

Biocapture surfaces produced for study of brain chemistry

Thu, 13 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) A research team at Penn State has developed a novel method for attaching small molecules, such as neurotransmitters, to surfaces, which then are used to capture large biomolecules. By varying the identity and spacing of the tethered molecules, researchers can make the technique applicable to a wide range of bait molecules including drugs, chemical warfare agents, and environmental pollutants. Ultimately, the researchers also hope to identify synthetic biomolecules that recognize neurotransmitters so that they can fabricate extremely small biosensors to study neurotransmission in the living brain.

In the brain, dozens of different small signaling molecules interact with thousands of large receptive proteins as part of the fundamental communication process between nerve cells. This cacophony of specific interactions is highly dependent on nanoscale molecular structure. One key to advancing our understanding of how the brain works is to identify the nature of the association between neurotransmitters and their binding partners. The technique of producing these high-affinity materials will be published in January 2008 in the journal Advanced Materials by a research team headed by Anne Milasincic Andrews, associate professor of veterinary and biomedical sciences, and including Paul S. Weiss, distinguished professor of chemistry and physics.

The process starts with a self-assembled monolayer (SAM), a single-molecule-thick layer that organizes itself on a surface. The molecules that make up the SAM terminate in and expose oligoethyleneglycol units that are known to prevent adhesion of proteins and other large biomolecules. Next, tether molecules are inserted into the defects that naturally occur in the SAM. Finally, a small molecule, in this case the neurotransmitter serotonin, is chemically linked to the tether molecules. Since the defects in the SAM occur at irregular but controllable intervals, serotonin molecules are prevented from clumping together. This is key to their being recognized by the correct proteins.

When the surface is exposed to a solution containing many different proteins, only those with high affinities for the tethered small molecule selectively attach to the surface. The bound protein molecules can then be identified in place or removed for characterization. The tethered neurotransmitter acts like a fishing pole, says Andrews. When the small molecule 'bait' is correctly placed on the surface, it captures much larger molecules that interact with it in a biologically specific way.

As a result of this inherent selectivity, it is possible to identify biomolecules, by function, from a sea of thousands of different types of molecules. Weiss adds, The key to obtaining a highly specific association is producing optimal spacing of the tethered neurotransmitters. The ideal spacing allows large molecules to recognize the functional groups of the small molecule while avoiding nonspecific binding to the surface itself.

Because of their selectivity, these materials are suitable for a variety of investigations in biological systems. Each neurotransmitter can bind to a number of different receptors in the brain, says Andrews. Some of these receptors are known, but there are many more to identify. Also, the numbers of receptors are altered in different disease states and in response to treatment, and these capture surfaces could be used to study how groups of functionally related proteins change in a coordinated fashion.

Dr. Nicholas Schiff receives research award for Innovation in Neuroscience

Thu, 13 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (Dec. 13, 2007) -- A leading authority on neurological disorders of consciousness, Dr. Nicholas Schiff of NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City has received a prestigious Research Award for Innovation in Neuroscience from the Society for Neuroscience, the world's largest organization of physicians and scientists who study the brain and nervous system.

The award -- for imaginative, innovative research that will advance novel ideas and have the potential to lead to significant breakthroughs in the understanding of the brain and nervous system and related diseases, -- was presented at the Society's recent annual meeting in San Diego.

Dr. Schiff was the lead author of a breakthrough study in the Aug. 2 journal Nature, reporting that a 38-year-old man who spent more than five years in a minimally conscious state as a result of a severe head injury is now communicating regularly with family members and recovering his ability to move after having his brain stimulated with pulses of electric current. The findings provide the first rigorous evidence that any procedure can initiate and sustain recovery in such a severely disabled person, years after the injury occurred.

Study investigators included NewYork-Presbyterian/Weill Cornell's Dr. Joseph Fins and physician-scientists at the JFK Johnson Rehabilitation Institute (Edison, N.J.) and the Cleveland Clinic Foundation.

Dr. Schiff is associate professor of neurology and neuroscience at Weill Cornell Medical College and associate attending neurologist at NewYork-Presbyterian/Weill Cornell. He is an inventor at Cornell University of some of the technology used in the study described in Nature and is a paid consultant and advisor to IntElect Medical Inc., to which the technology has been licensed by Cornell University and in which Cornell University has an equity interest. A Conflict Management Plan relating to IntElect and its relationship with Dr. Schiff and Cornell University is in place.

A diplomate of the American Board of Psychiatry and Neurology, he received his medical degree from Cornell University Medical College (now Weill Cornell Medical College). He completed his residency in neurology at The New York Hospital (now NewYork-Presbyterian/Weill Cornell), where he trained with Drs. Fred Plum and Jerome Posner and developed his subspecialty interest in the field of impaired consciousness. He is a co-author of the fourth edition of Dr. Plum and Posner's classic textbook The Diagnosis of Stupor and Coma. Dr. Schiff is an elected member of the American Neurological Association. His long-range goals are to develop strategies and improved diagnostics to treat of chronic cognitive disabilities resulting from brain injuries.

Breakthrough technology observes synapse in real time, supporting theory of vesicular recycling

Thu, 13 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (Dec. 13, 2007) -- For the first time, scientists at Weill Cornell Medical College in New York City have observed in real time a cellular mechanism that's crucial to how brain cells communicate.

In doing so, they've also laid to rest a competing theory as to how key cellular processes -- called endocytosis and exocytosis -- work.

The scientists published their findings in this week's online edition of Proceedings of the National Academy of Sciences (Dec. 18 print edition).

Healthy neurological function hinges on the efficient passage of information between brain cells via the synapse, and exocytosis/endocytosis is the complex trafficking mechanism that allows this to happen.

At its simplest level, exocytosis involves the packaging, transport and delivery of neurotransmitter chemicals in sac-like structures called vesicles. These vesicles move from the interior of the cell to the cell membrane, where they deliver their information-rich cargo to the synapse. Endocytosis involves a similar function in the reverse direction, with incoming vesicles being transported into the cell's interior.

The vesicles aren't discarded, however. Instead, once they release their cargo they are recycled for use in another go-round. There have been two competing theories about how that recycling occurs -- either the vesicle fragments upon delivering its cargo and must be rebuilt, or it simply empties itself like milk from a bottle which is then resealed.

The vast bulk of the evidence suggests the former theory is actually the correct one, but it's been tempting to think of the 'resealable spout' theory, because it seems so logical and because there's been some ambiguous evidence that it might be true, says the study's co-author Dr. Timothy Ryan, professor of biochemistry at Weill Cornell Medical College.

The trouble is, no one had ever found a way to observe -- accurately and in real time -- synaptic vesicle recycling as it occurs.

That has changed with this new paper. We have taken advantage of recent advances in fluorescent 'tagging' of molecules involved in these cellular processes, as well as new microscopy technologies that give us an incredible new ability to watch all of this, up close and in real-time, says Dr. Ryan.

Specifically, Dr. Ryan used a fluorescent chemical stain called pHluorin and genetically fused it to a vesicular protein called vGlut1. We've used this fluorescent tagging approach before, but with molecules that can exist on either the outside or the inside of the vesicle, Dr. Ryan notes.

VGlut1 gives us a much more precise view, since it only inhabits the inside of the vesicle, he adds. That means that when we see the green fluorescent tag move outside of the vesicle, then the vesicle itself must have ruptured in some way. This gives us a much more accurate picture of the recycling process.

At the same time, the team took advantage of new breakthroughs in optical microscopy that maximize how much of the tag's fluorescent light can be grabbed by the microscope. This approach allowed them, for the first time, to follow how individual synaptic molecules are delivered and retrieved from the synaptic surface.

The result is an accurate view into this hitherto mysterious synaptic phenomenon, Dr. Ryan says.

The resealable spout hypothesis of vesicular recycling (also known as the kiss-and-run theory) may be the first casualty of this new insight.

We observed that, although recycling appears to occur within a set but somewhat variable time-frame, it's still using the same mechanism -- the vesicle falls apart upon delivering its cargo to the cell membrane, and then enzymes go to work re-building it for the next cycle, Dr. Ryan adds. I think this real-time observation really closes the door on the 'kiss-and-run' theory of vesicular recycling.

The new technology used in these experiments should bring scientists much more insight into how the synapse works generally, and that could have real implications for our understanding of neurological health and illness, Dr. Ryan says.

This is all part of the 'shop manual' of neurological function that we are currently putting together, piece by piece, he says. Discoveries like these are adding new pages to the manual every day, and it's that kind of knowledge that will someday save, extend and improve lives.

In fruit flies, homosexuality is biological but not hard-wired

Sun, 09 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) While the biological basis for homosexuality remains a mystery, a team of neurobiologists reports they may have closed in on an answer -- by a nose.

The team led by University of Illinois at Chicago researcher David Featherstone has discovered that sexual orientation in fruit flies is controlled by a previously unknown regulator of synapse strength. Armed with this knowledge, the researchers found they were able to use either genetic manipulation or drugs to turn the flies' homosexual behavior on and off within hours.

Featherstone, associate professor of biological sciences at UIC, and his coworkers discovered a gene in fruit flies they called genderblind, or GB. A mutation in GB turns flies bisexual.

Featherstone found the gene interesting initially because it has the unusual ability to transport the neurotransmitter glutamate out of glial cells -- cells that support and nourish nerve cells but do not fire like neurons do. Previous work from his laboratory showed that changing the amount of glutamate outside cells can change the strength of nerve cell junctions, or synapses, which play a key role in human and animal behavior.

But the GB gene became even more interesting when post-doctoral researcher Yael Grosjean noticed that all the GB mutant male flies were courting other males.

It was very dramatic, said Featherstone. The GB mutant males treated other males exactly the same way normal male flies would treat a female. They even attempted copulation.

Other genes that alter sexual orientation have been described, but most just control whether the brain develops as genetically male or female. It's still unknown why a male brain chooses to do male things and a female brain does female things. The discovery of GB provided an opportunity to understand why males choose to mate with females.

Based on our previous work, we reasoned that GB mutants might show homosexual behavior because their glutamatergic synapses were altered in some way, said Featherstone. Specifically, the GB mutant synapses might be stronger.

Homosexual courtship might be sort of an 'overreaction' to sexual stimuli, he explained.

To test this, he and his colleagues genetically altered synapse strength independent of GB, and also fed the flies drugs that can alter synapse strength. As predicted, they were able to turn fly homosexuality on and off -- and within hours.

It was amazing. I never thought we'd be able to do that sort of thing, because sexual orientation is supposed to be hard-wired, he said. This fundamentally changes how we think about this behavior.

Featherstone and his colleagues reasoned that adult fly brains have dual-track sensory circuits, one that triggers heterosexual behavior, the other homosexual. When GB suppresses glutamatergic synapses, the homosexual circuit is blocked.

Further work showed precisely how this happens -- without GB to suppress synapse strength, the flies no longer interpreted smells the same way.

Pheromones are powerful sexual stimuli, Featherstone said. As it turns out, the GB mutant flies were perceiving pheromones differently. Specifically, the GB mutant males were no longer recognizing male pheromones as a repulsive stimulus.

Featherstone says it may someday be possible to domesticate insects such as fruit flies and manipulate their sense of smell to turn them into useful pollinators rather than costly pests.

Smell experience during critical period alters brain

Wed, 05 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Unlike the circuitry of the visual system, that of the olfactory system was thought to be hardwired: Once the neurons had formed, no amount of sensory input could change their arrangement. Now researchers at Rockefeller University and their collaborators have upturned this scientific dogma by showing that there is a sensitive period during which the external environment can alter a circuit in the fly brain that detects carbon dioxide, a gas that alerts flies to food and mates. This research, to be published in the December 6 issue of Neuron, may suggest that this brain plasticity isn't limited to the carbon dioxide detection circuit. Rather, it may be a general feature of the olfactory system itself.

The circuit has a genetic plan, but that genetic plan can adjust to real world conditions, says Leslie Vosshall, head of the Laboratory of Neurogenetics and Behavior. This paper is the first compelling case that the olfactory system is plastic.

Using several imaging techniques, Vosshall and her colleagues traced the carbon dioxide circuit, a well-described pathway that consists of three different types of neurons, the axons and dendrites of which form an entangled ball called a glomerulus. The researchers exposed flies to elevated levels of carbon dioxide to see whether it would alter the shape of this circuit or how it functioned. The glomerulus's volume was already increased after two days of exposure (from birth) and kept on increasing for five days, at which point it stopped. The increase in this specific glomerulus could only be induced by elevated levels of carbon dioxide and was also reversible.

After those initial few days, however, the researchers saw a different story unfold. If they didn't expose the flies to carbon dioxide within the first five days, genetics locked in the glomerulus's size such that no matter how long the flies were exposed to the gas, the glomerulus's volume didn't increase. These findings suggest that the fly's external environment can rewire the carbon dioxide detection circuit only during a five-day window of development.

During this critical period, the olfactory system is flexible enough to calibrate its genetic map to its local environment, says first author Silke Sachse, a former postdoc in the Vosshall lab who is now a group leader in optical imaging at the Max Planck Institute for Chemical Ecology in Jena, Germany. But once that window closes, the circuit is no longer plastic.

To figure out the mechanism by which the glomerulus increases its volume, the Vosshall group imaged the three types of neurons that make up the glomerulus -- olfactory sensory neurons, projection neurons and interneurons -- to see whether their structure or function had changed. The olfactory sensory neurons, which report sensory information to glomeruli, did not show any sign of structural or functional changes. However, the projection neurons, which send information from the glomeruli to the brain, and the interneurons, which communicate with the two types of neurons as well as the glomeruli, showed significant functional changes. Usually the sensory neurons collect information and send it to the brain and it is the job of the brain to interpret what the information means, says Vosshall. For plasticity to be useful, it probably makes sense to delegate that job to the brain rather than to the external sensory neurons.

Pheromones identified that trigger aggression between male mice

Wed, 05 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) A family of proteins commonly found in mouse urine is able to trigger fighting between male mice, a study in the Dec. 6, 2007, issue of Nature has found. The study, which is the first to identify protein pheromones responsible for the aggression response in mice, was funded in part by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health. Pheromones are chemical cues that are released into the air, secreted from glands, or excreted in urine and picked up by animals of the same species, initiating various social and reproductive behaviors.

Although the pheromones identified in this research are not produced by humans, the regions of the brain that are tied to behavior are the same for mice and people. Consequently, this research may one day contribute to our understanding of the neural pathways that play a role in human behavior, says James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. Much is known about how pheromones work in the insect world, but we know very little about how these chemicals can influence behavior in mammals and other vertebrates.

Researchers at Scripps Research Institute, La Jolla, Calif., and Harvard University chose to study aggression for this study because it is a strongly exhibited social behavior in male mice. Because mouse urine had already been linked to aggressive behavior in males, the team narrowed the field of pheromone candidates by separating out progressively smaller compounds in the urine and studying their effects on both mouse behavior and their ability to activate sensory receptor neurons in the vomeronasal organ. The vomeronasal organ is one of two locations in the mouse's nasal cavity that houses sensory receptor cells that detect pheromones. The other location is the main olfactory epithelium, the part of the nasal cavity that also detects smells. Earlier research conducted by the group had determined that receptor neurons from the vomeronasal organ are required for the aggression response to occur.

To study behavior, the researchers swabbed the backs of neutered male mice with the various pheromone candidates and placed them in a cage with a normal male mouse. Neutered males are useful for the study of aggression because they can neither emit nor detect the aggression pheromones. Whereas normal males will begin fighting as soon as they are placed together in a cage, neutered males remain docile around normal males, and vice versa. If a neutered male whose back has been swabbed with a pheromone candidate elicits hostility in a normal male, the researchers know that the pheromone candidate is responsible for the behavior.

Using a technique called calcium imaging, the team also studied whether pheromone candidates were able to directly activate sensory receptor neurons. Receptor neurons were removed from a mouse vomeronasal organ, spread out on a Petri dish, and labeled with a substance that changed color when the neuron was activated.

The researchers discovered that the protein family that comprises the major urinary protein (MUP) complex in mouse urine is one of two pheromones that can elicit the aggression response in male mice. They also found that the MUP protein is recognized exclusively in the vomeronasal organ, not in the main olfactory epithelium, and activates a specific type of sensory receptor neuron. A second pheromone was also found to elicit an aggression response in male mice, however further study needs to be done regarding its make-up and activity.

There are about 20 members of the MUP family, and each mouse expresses four to six of the members randomly, explains senior investigator Lisa Stowers, Ph.D. This creates a bar code of individuality for each mouse. And we don't know whether the proteins are actually coding for aggression per se, or whether they're serving as a general cue of individuality for a male.