Friday, June 20, 2008

Risk factors for sudden death for adult muscular dystrophy identified

The largest assessment of people with adult muscular dystrophy has identified risk factors that can lead to sudden death for individuals with the most common form of this disease.

The results of the multicenter study, lead by the Indiana University School of Medicine, are reported in the June 19 issue of the New England Journal of Medicine.

Neurologists and cardiologists at 23 neuromuscular disease clinics nationwide affiliated with the Muscular Dystrophy Association assessed 406 adult patients with myotonic dystrophy type 1 using clinical history, genetic assessment and electrocardiograms (ECG) to determine the risk factors that cause arrhythmias and sudden cardiac death.

"The study has prospectively identified risk factors that predict a high risk of sudden death in people with myotonic dystrophy, the most common form of muscular dystrophy that we see in adults," said the study's principal investigator and lead author William J. Groh, M.D., M.P.H., associate professor of medicine at the Indiana University School of Medicine and the Krannert Institute of Cardiology. Sudden death is defined as a death that occurs in a stable patient within one hour of the onset of symptoms.

During the 10 years of the study, 20 percent of the people enrolled died, said Dr. Groh. Of those, one-third died of sudden death likely attributable to cardiac arrhythmia.

"Patients who had significant abnormalities on their ECG were at a 3.5 times higher risk of sudden death," said Dr. Groh. "Those with atrial (upper) chamber arrthymias had a 5 times higher risk."

In the future, physicians can use these risk factors to evaluate patients with myotonic dystrophy to hopefully prevent sudden death through further evaluation including electrophysiological studies (using catheters in the heart) or by surgically implanting a cardioverter-defibrillator.

Dr. Groh said another important outcome of the study was the discovery that pacemakers, commonly used to treat some forms of arrhythmia, did not help these patients prevent sudden death.

Myotonic muscular dystrophy, an inherited disease, is characterized primarily by progressive muscle weakness and muscle wasting. It affects approximately 1 of every 8,000 people in the United States.

In many muscular dystrophies, the heart muscle is adversely affected. Those heart abnormalities can be as serious and debilitating as the skeletal muscle involvement more commonly associated with muscular dystrophy.

This study was funded by Medtronic, the Muscular Dystrophy Association and the National Institutes of Health.

http://www.iupui.edu

Monday, June 9, 2008

How best to treat chronic pain? The jury is still out

How best to alleviate chronic pain, a leading cause of disability and employee absenteeism, continues to perplex both patients and their doctors.

A review of recent studies on pain medicine appearing in the June 2008 issue of the Journal of General Internal Medicine reports that while various approaches and combinations of therapies to treat pain have advantages and disadvantages, researchers don't yet know how to determine which is best for individual patients.

Among the approaches to pain management studied were those relying on the prescription of opioids (drugs such as morphine, Percocet and Vicodin), surgery, and alternative medicine (acupuncture, herbal remedies).

"We conducted this review of pain management strategies because doctors, especially primary care doctors who manage the bulk of patients with chronic pain, are frustrated and want to know how to better alleviate what is often debilitating pain. Many of these physicians have not been well trained in pain management. And while many are paying more attention to pain than ever before, especially given JCAHO (Joint Commission on Accreditation of Healthcare Organizations) and Veteran Affairs mandates that pain be regarded as the 'fifth vital sign,' they don't know what treatment will work for a given patient. They want guidance and we found very limited information," said the paper's senior author, Matthew J. Bair, M.D. Dr. Bair is an assistant professor of medicine at the Indiana University School of Medicine, a research scientist with the Regenstrief Institute, Inc. and an investigator at the Roudebush VA Center of Excellence for Implementing Evidence Based Practice.

Chronic or recurrent pain affects more than 75 million Americans.

"We have found that there are huge gaps in our knowledge base. For example, none of the opioid research trials lasted longer than four months, a small fraction of the time during which many chronic sufferers typically experience pain and are prescribed this potent class of medication," said Dr. Bair. "Similarly there were insufficient trials of herbal remedies versus other analgesics (i.e. pain medicines), in spite of the fact that pain management is one of the major reasons for the use of alternative medicine."

Dr. Bair's own research focuses on understanding the interface between affective disorders such as depression and anxiety and chronic pain and developing strategies to improve pain management in the primary care setting.

http://www.iupui.edu

Thursday, June 5, 2008

Saving teeth by using periodontal ligament regeneration

Teeth may fall out as a result of inflammation and subsequent destruction of the tissues supporting the teeth. Dutch researcher Agnes Berendsen has investigated a possible solution to this problem. At the Academic Centre for Dentistry Amsterdam (ACTA), she has studied the regeneration of the periodontal ligament by use of tissue engineering.

The 3D in vitro model she has developed appears to be promising for regenerating periodontal ligament and may also prove valuable for restoring tendons and ligaments elsewhere in the body.

The periodontal ligament forms a flexible connection between the tooth root and the surrounding jaw bone. Trauma or inflammation can cause destruction of the periodontal ligament. Berendsen chose tissue engineering to tackle this problem. Research in tissue engineering uses cells placed in a 3D model, after which signals are applied to activate the cells. Berendsen developed a new 3D model in which cells isolated from periodontal ligament were implanted in a collagen network suspended between an artificial root and artificial bone. She wanted to see if viable periodontal ligament could be generated in this way.

The composition of the collagen network in which the cells are located has a considerable influence on the contractile properties of the cells. Contraction of the cells creates internal tension in the network which keeps the cells active. The network must be well attached to the surrounding solid surfaces to prevent its detachment. Berendsen managed to attach the network to these artificial root and bone surfaces present in the model by creating an enzyme-mediated mineral deposition on the surfaces. By subsequently applying loading to the tooth root (mimicking the process of chewing) in the 3D model, she was able to deform the mineral-anchored network containing the cells. The subsequent response of the cells was dependent on the magnitude of the loading.

Follow-up research will investigate whether the cell-culture results can be translated to an animal model to obtain more accurate insights concerning the potential use of this method in humans.

http://www.nwo.nl/

Tuesday, June 3, 2008

Happy children may not be best learners

Psychologists at the University of Virginia and the University of Plymouth (UK) have conducted experimental research that contrasts with the belief that happy children are the best learners.

The findings, which currently appear online in the journal Developmental Science and will be printed in the June issue, show that where attention to detail is required, happy children may be at a disadvantage.

The researchers conducted a series of experiments with different child age groups who had happy or sad moods induced with the aid of music (Mozart and Mahler) and selected video clips (Jungle Book and the Lion King). The groups were then asked to undertake a task that required attention to detail - to observe a detailed image such as a house and a simple shape such as a triangle, and then locate the shape within the larger picture. The findings in each experiment with both music and video clips were conclusive, with the children induced to feel a sad or neutral mood performing the task better than those induced to feel a happy state of mind.

Lead researcher Simone Schnall of the University of Plymouth describes the psychology behind the findings: "Happiness indicates that things are going well, which leads to a global, top-down style of information processing. Sadness indicates that something is amiss, triggering detail-orientated, analytical processing.

"However, it is important to emphasize that existing research shows there are contexts in which a positive mood is beneficial for a child, such as when a task calls for creative thinking. But this particular research demonstrates that when attention to detail is required, it may do more harm than good."

Co-author Vikram Jaswal, an assistant professor of psychology at the University of Virginia, added that the findings contradict conventional wisdom that happiness always leads to optimal outcomes. "The good feeling that accompanies happiness comes at a hidden cost. It leads to a particular style of thinking that is suited for some types of situations, but not others."

http://www.virginia.edu/

Chronic inflammation of the intestine or stomach damages DNA

Chronic inflammation of the intestine or stomach can damage DNA, increasing the risk of cancer, MIT scientists have confirmed.

The researchers published evidence of the long-suspected link in the June 2 online issue of the Journal of Clinical Investigation (JCI).

In two studies, the researchers found that chronic inflammation accelerated tumor formation in mice lacking the ability to repair DNA damage.

"It's something that was expected but it was never formally proven," said Lisiane Meira, research scientist in MIT's Center for Environmental Health Sciences (CEHS) and lead author of the paper.

The results of this work suggest that people with decreased ability to repair DNA damage might be more susceptible to developing cancer associated with chronic inflammation such as ulcerative colitis, Meira said.

Inflammation caused by infectious agents such as Helicobacter pylori and Hepatitis C is known to increase the risk of stomach and liver cancers, respectively. Researchers have long known that inflammation produces cytokines (immune response chemicals that encourage cell proliferation and suppress cell death), which can lead to cancer.

In addition, it was suspected that another effect of the inflammation pathway could also induce cancer. During the inflammatory response to infection, immune cells such as macrophages and neutrophils release reactive oxygen and nitrogen species that can damage DNA.

Under normal circumstances, the DNA damage induced during an inflammatory response is repaired by DNA repair systems. But, if the DNA repair system is not functioning properly, that damage can induce mutations that can lead to cancer, according to the new study.

Every individual has variations in the effectiveness of their DNA repair systems, which could help doctors figure out which patients are most susceptible to inflammation-induced cancers.

"That variation could influence the susceptibility of individuals and how they are going to respond to a chronic inflammation response," said Leona Samson, senior author of the study and director of the CEHS.

In the JCI study, the researchers induced colon inflammation in the mice by treating them with a chemical compound that creates a condition similar to human colitis. "Lo and behold, the DNA repair deficient mice were more susceptible" to cancer, said Meira.

To show that this is a general phenomenon, the team did a second study, in collaboration with another CEHS member, James Fox, director of the Division of Comparative Medicine at MIT, and one of his students, Chung-Wei Lee. They showed that mice infected with H. pylori, who also lacked the proper DNA repair mechanisms, were more susceptible to pre-cancerous lesions in the stomach.

This study is related to another recent paper published by Fox, which found that treating H. pylori infection early with antibiotics can prevent cancer development. The new study suggests that if H. pylori goes untreated, patients with poorly functioning DNA repair mechanisms would have a greater risk of developing cancer.

http://web.mit.edu/

Friday, May 30, 2008

Wireless vision implant

About 30 million people around the world have grown legally blind due to retinal diseases. The EPI-RET project has sought for a technical solution for the past twelve years to help these patients. This work has resulted in a unique system - a fully implantable visual prosthesis.

For twelve years, experts from different disciplines in the fields of microelectronics, neurophysics, information engineering, computer science, materials science and medicine have been working to develop a visual prosthetic device for patients who have lost their sight through diseases of the retina. In September 2007, their effort was rewarded. In a clinical study including six patients, the team was able to demonstrate not only that a completely implantable vision prosthesis is technically feasible and proven functioning, but also that it enables patients to perceive visual images. "For normally sighted people that may not seem much, but for the Blind, it is a major step," comments Dr. Hoc Khiem Trieu from the Fraunhofer Institute for Microelectronic Circuits and Systems IMS in Duisburg. "After years of blindness, the patients were able to see spots of light or geometric patterns, depending on how the nerve cells were stimulated." Dr. Hoc Khiem Trieu has been involved from the outset of this project, which was funded by the German Ministry of Education and Research. Together with Dr. Ingo Krisch and Dipl.-Ing. Michael Görtz he translated the specifications given by the medical experts and material scientists into an implant and chip design. The scientists are to receive the Joseph von Fraunhofer Prize 2008 for their work.

"A milestone was reached when the prosthetic system finally operated wirelessly and remotely controlled," explains Dr. Ingo Krisch. "A great deal of detailed work was necessary before the implant could be activated without any external cable connections." "The designs became smaller and smaller, the materials more flexible, more robust and higher in performance, so that the implant now fits comfortably in the eye," reports Michael Görtz. The system benefits from a particular disease pattern, and it uses a specific operating principle to restore sight: Suffering from retinitis pigmentosa, the light sensitive cells are destroyed, but the connection of the nerve cells to the brain remains intact. The scientists have bypassed the defects of the retina by means of a visual prosthesis. The complete system comprises the implant and an external transmitter integrated in a spectacle-frame. The implant system converts the image patterns into interpretable stimulation signals. Data and energy are transferred to the implant by a telemetric link. The nerve cells inside the eye are then stimulatedaccording to the captured images. Those intact cells are innervated by means of three-dimensional stimulation electrodes that rest against the retina like small studs.

http://www.fraunhofer.de

New type of wound dressing made of silica gel fibers

A new type of wound dressing made of silica gel fibers will soon help to heal difficult wounds caused by burns or diabetes. The dressing forms a supporting matrix for newly growing skin cells and is fully absorbed by the body during the healing process.

In Germany alone, about three million - mostly elderly - patients suffer from poorly healing large-area wounds caused by complaints such as diabetes, burns or bedsores. The wounds can be treated with conventional collagen dressings or polylactic acid dressings, but the success rate is not as good as it should be. A new type of dressing made of silica gel fibers, developed by scientists at the Fraunhofer Institute for Silicate Research ISC in W?g, shall solve the problem. This novel dressing has many advantages: it is shape-stable, pH-neutral and 100 percent bioresorbable. Once applied it remains in the body, where it gradually degrades without leaving any residues. What's more, the fibre fleece provides the healthy cells around the edges of the wound with the structure they additionally need for a proper supply of growth-supporting nutrients. To prevent any infection, treatment of the wound must be absolutely sterile. "As only the outer bandage needs to be changed, the risk of contaminating the wound is low," explains Dr. Jörn Probst of the ISC. And thanks to the supporting matrix for the cells, the chances of a scar-free natural closure of the wound are very good.

The fibers are produced by means of wet-chemical material synthesis, a sol-gel process in which a transparent, honey-like gel is produced from tetraethoxysilane (TEOS), ethanol and water in a multi-stage, acidically catalyzed synthesis process. The gel is processed in a spinning tower: "We press it through fine nozzles at constant temperatures and humidity levels," explains Walther Glaubitt, the inventor of the silica gel fibers. "This produces fine endless threads which are collected on a traversing table and spun in a specific pattern to produce a roughly A4-sized multi-layer textile web." The dressings are then cut, packed and sterilized. Dr. Jörn Probst and Dipl.-Ing. Walther Glaubitt will receive the Joseph von Fraunhofer Prize 2008 for developing the biocompatible dressing.

A partner to support the development and market the dressing has already been found: Bayer Innovation GmbH BIG, a wholly owned subsidiary of Bayer AG. "We anticipate that hospitals will start to use the silica gel wound dressing in 2011," states Iwer Baecker, project manager at Bayer Innovation GmbH. And that is by no means the end of the story. The scientists plan to integrate active substances such as antibiotics or painkillers in the dressing to improve and accelerate the healing process.

http://www.fraunhofer.de

Lack of dental care may have life-threatening implications

New research from the University of Bristol shows that admissions for the surgical treatment of dental abscess have doubled in the last ten years despite the fact that these serious infections are preventable with regular dental care.

The findings, published in the British Medical Journal today, could reflect a decline of oral health, changes in access to dental treatment or changes in attitudes to dental care.

The analysis was conducted by Dr Steve Thomas and colleagues from the Division of Maxillofacial Surgery and Department of Oral and Dental Science using routine NHS data on hospital admissions and was prompted by three complex cases of dental abscess that presented over a six-month period in 2006. The case studies, provided in full below, highlight the serious and potentially life-threatening consequences of dental abscesses. In two of the cases the patients needed to be admitted to a hospital critical-care unit; none of the three was registered with a dentist.

Recent surveys report improvements in oral health, so an explanation for the increase in hospital admissions is required. The paper suggests it could be linked to changes to dentists' remuneration in the 1990s, which led many to reduce their NHS workload, and a corresponding decline in the number of adults in England registered with an NHS dentist from 23 million in 1994 to approximately 17 million in 2003/04. These changes may have resulted in reductions in the provision of routine dental care and reduced access to emergency dental care and may explain the rise in surgical admissions.

An alternative explanation is that the problem lies with people not seeking dental care but a recent survey of 5,200 members of the public and 750 dentists, conducted by the Commission for Patient and Public Involvement in Health, found that 22% of people had declined treatment because of high cost, and 84% of dentists felt that their new contract had failed to improve access to NHS services.

The authors recommend that access to routine and emergency dental care be reviewed and formal and robust systems of referral established to ensure that GPs can be confident that patients presenting to them with acute dental sepsis will receive appropriate dental treatment.

Speaking about the findings, Dr Thomas said:

'Dental abscess is a serious problem and can be life threatening. In the past ten years the incidence of dental abscesses requiring surgical drainage in hospital has doubled. The reasons for this increase need to be identified and robust measures taken to ensure the epidemic is controlled.'

Further information:

Case study 1

In March 2006 a 48-year-old woman was referred by her GP to the A&E department of Bristol Royal Infirmary with a swelling beneath the jaw bone in her neck that was diagnosed as an abscess. She was prescribed antibiotics and the abscess drained. Two days later she was breathing rapidly, had low blood pressure and low urine output. A scan showed she had fluid from the neck to the diaphragm. She underwent surgery and pus was drained from around her trachea and heart. She was transferred to the Critical Care Unit for treatment and was diagnosed as having Adult Respiratory Distress Syndrome. She spent 22 days on the Critical Care Unit and a further 22 days on the surgical ward. She was not registered with a dentist.

Case study 2

In May 2006 a 48-year-old-man presented to the A&E Department at Frenchay Hospital, Bristol with a swelling beneath the jaw bone in his neck that was diagnosed as a dental abscess. He was not registered with a dentist. He was advised to find a dentist and request treatment. He was unable to find a dentist and returned to the same A&E department three days later. He was given antibiotics and again advised to seek dental treatment. A day later his partner found him in a coma. He was admitted to the Critical Care Unit where he was diagnosed with diabetic keto-acidosis (a diabetic condition which can lead to coma) and the neck abscess drained. He was ventilated and dialysed and spent three weeks in the Critical Care Unit.

Case study 3

In July 2006 a 41-year-old woman saw her GP because of swelling on the left side of her face. It was diagnosed as mumps. One week later she presented to the A&E department of Bristol Royal Infirmary with an abscess. The wound was cleaned and drained and antibiotics were prescribed. The patient was not registered with a dentist.

The paper, 'Is there an epidemic of admissions for surgical treatment of dental abscesses in the UK?' by Steven J. Thomas, Charlotte Atkinson, Ceri Hughes, Andrew R. Ness is published today in the British Medical Journal.

The study looked at Hospital Episode Statistics (HES) data on all admissions to NHS hospitals in England for each year from 1998/99 to 2005/06. This dataset includes information on private patients treated in NHS hospitals, patients who were resident outside of England, and patients where care was funded by the NHS but delivered by treatment centres (including those in the independent sector).

These national data are consistent with a recent audit carried out at the Hull Royal Infirmary that showed an increase in the number of patients presenting to oral and maxillofacial surgery services with dental sepsis (from 17 to 25) between 1999 and 2004. A similar audit of services at Leeds General Infirmary, conducted between 2000 and 2005, did not show such an increase. Both audits were based on small numbers of cases.

The National Institute for Clinical Excellence recommends that adults should have regular dental check ups every three to 24 months.

http://www.bris.ac.uk/

Thursday, May 29, 2008

Do people from different countries behave differently in a crisis?

Professor Ed Galea, from the University of Greenwich in London, and a team of international colleagues have won a grant of 2 million Euros from the European Union. The University of Greenwich has a 500,000 Euro share of the funding, the largest research budget of the eight partners in the project team.

In this study, Professor Galea, an expert in fire safety engineering, will compare how people behave when fleeing from emergencies in seven countries: Germany, Spain, Sweden, Turkey, Poland, the UK and the Czech Republic. They will conduct evacuation trials in each country, using people of similar age and occupation, and the same type of building.

Professor Galea says: "If fire breaks out on a plane, in a building or on a ship, how long will it take the occupants to get out? And do people from different countries behave differently in a crisis? This research asks whether culture and ethnicity play a role in determining how people respond in disasters. Our findings will give us confidence to predict how people will behave in emergencies, knowing that our computer models are based on how real people behave.

"This is important as all parts of the world are vulnerable to emergency incidents. There have been terrorist attacks on the World Trade Centre, the Madrid train system and the London underground. There have been natural disasters such as earthquakes in Turkey and Japan. And devastating fires have caused deaths in many countries."

Ed Galea is a world expert on modelling fires and how people behave in emergencies. His expertise has helped to design safer structures around the world including the Sydney Olympic Stadium, the O2 Dome, Arsenal's Emirates Stadium, Airbus A380 and the new aircraft carriers for the Royal Navy. His software was also used by the US government authority charged with investigating the World Trade Centre 9/11 evacuation and he is currently completing work on a £1.5 million EPSRC project interviewing survivors of the disaster.

The Fire Safety Engineering team at the University of Greenwich, which is headed by Ed Galea, has won the Queen's Anniversary Award for Higher & Further Education, the British Computer Society's IT Award and the European Information Society Technologies prize.

This project, Behaviour, Security & Culture (BeSeCU) has been funded under the EU's Seventh Framework Programme. It is led by the Institute of Medical Psychology in Hamburg, Germany.

Professor Tom Barnes, Pro Vice-Chancellor (Research & Enterprise) at the University of Greenwich, says: "We are delighted that the EU is to fund this project involving our internationally-renowned Fire Safety Engineering Group. Bringing together the expertise of engineers, computer modellers and psychologists, the team takes a multi-disciplinary approach to find solutions to real-world problems - an excellent example of the research mission of this university."

Members of the university's Fire Safety Engineering Group have also just won a prestigious international prize. The US Society of Fire Protection Engineers has chosen them as winners of the Jack Bono Engineering Communication Award, which recognises the research paper that has most contributed to the advancement and application of professional fire protection engineering. The winning publication from the Greenwich team appeared in the Journal of Fire Protection Engineering last year, The winning paper from the Greenwich team appeared in the Journal of Fire Protection Engineering last year, entitled "Signage Legibility Distances as a Function of Observation Angle" and was authored by Hui Xie, Lazaros Filippidis, Steven Gwynne, Edwin Galea, Darren Blackshields and Peter Lawrence.

http://www.gre.ac.uk/

Friday, May 23, 2008

Real-time observation of the DNA-repair mechanism

For the first time, researchers at Delft University of Technology have witnessed the spontaneous repair of damage to DNA molecules in real time.

They observed this at the level of a single DNA molecule. Insight into this type of repair mechanism is essential as errors in this process can lead to the development of cancerous cells. Researchers from the Kavli Institute of Nanoscience Delft are to publish an article on this in the leading scientific journal Molecular Cell.

Cells have mechanisms for repairing the continuous accidental damage occurring in DNA. These damages can vary from a change to a single part of the DNA to a total break in the DNA structure. These breaks can, for instance, be caused by ultraviolet light or X-rays, but also occur during cell division, when DNA molecules split and form two new DNA molecules. If this type of break is not properly repaired it can be highly dangerous to the functioning of the cell and lead to the creation of a cancerous cell.

One major DNA-repair mechanism involved in repairing these breaks is known as homologous recombination. This mechanism has been observed for the first time by Delft University of Technology researchers in real time and at the level of a single DNA molecule.

To observe this, a DNA molecule is stretched between a magnetic bead and a glass surface. A force is exerted on the magnetic bead using a magnetic field, enabling researchers to pull and rotate a single DNA molecule in a controlled fashion. As the position of the bead changes when the DNA molecule is repaired, researchers are able to observe the repair process in detail.

http://home.tudelft.nl/en/

Thursday, May 22, 2008

Smoking is addictive, but quitting is contagious

Over the last 30 years, the number of smokers in the U.S. has steadily decreased-a tribute to the efforts of public-health workers everywhere. And while this fact is unarguable, less obvious are the social and cultural forces that lead an individual to kick the habit. In fact, when someone crumbles that last empty pack of their favorite unfiltered brand and vows to never buy another, he might not realize that he is less like the heroic individual grasping his own boot straps and more like a single bird whose sudden left turn is just one speck in the larger flock.

These are the findings of a massive longitudinal study spanning 32 years: people quit smoking in droves. Through reconstructing the social network of 12,067 individuals, researchers from Harvard Medical School and the University of California, San Diego have discovered that smoking cessation occurs in network clusters and is hardly the isolated decision it might feel like to the individual quitter.

"We've found that when you analyze large social networks, entire pockets of people who might not know each other all quit smoking at once," says Nicholas Christakis, a professor in Harvard Medical School's Department of Health Care Policy, who, along with U.C. San Diego researcher James Fowler, authored the study. "So if there's a change in the zeitgeist of this social network, like a cultural shift, a whole group of people who are connected but who might not know each other all quit together."

The study, which was funded primarily by the National Institute on Aging, appears in the May 22 issue of the New England Journal of Medicine.

Over the last few years, Christakis, who is also a professor of sociology in the Faculty of Arts and Sciences at Harvard University, and Fowler have been analyzing data from the Framingham Heart Study (an ongoing cardiovascular study begun in 1948), recreating the social patterns contained within the study data to see how health correlates with an individual's social network.

The researchers derived information from archived, handwritten administrative tracking sheets dating back to 1971. All family changes for each study participant, such as birth, marriage, death, and divorce, were recorded. In addition, participants had also listed contact information for their closest friends, as well as coworkers and neighbors. Coincidentally, many of these friends and coworkers were also study participants. Focusing on 5,124 individuals, Christakis and Fowler observed a total of 53,228 social, familial, and professional ties.

Last year, they reported on how obesity spreads through social networks. Using the same data, they decided to analyze smoking cessation trends within that same population.

The first and most striking finding was the discovery that, from the larger network perspective, people quit smoking as groups and not as individuals.

"When you look at the entire network over this 30-year period, you see that the average size of each particular cluster of smokers remains roughly the same," says Fowler. "It's just that there are fewer and fewer of these clusters as time goes on."

They were able to quantify the person-to-person effects of smoking cessation among married couples, siblings, friends, and coworkers. In addition, they also discovered "quitting cascades" that advanced from person-to-person-to-person. (See end of release for statistical chart.)

Christakis illustrates this point by describing a small network containing three individual smokers, persons A, B, and C. The first person, A, is friends with B, and B is friends with C, but A and C do not know each other. If C quits smoking, A's chances of not smoking spike 30 percent, regardless of whether or not B smokes. The middle individual, it would appear, might act as a kind of "carrier" for a social norm.

Education also seems to matter. We are more influenced by the quitting behavior of others if those people are highly educated. To add a further twist, we are also more influenced by others if we ourselves are more educated.

Says Christakis, "We see by this that the educated are not only more influential, but they are also more easily influenced."

And finally, Christakis and Fowler discovered that smokers are increasingly marginalized throughout social networks.

"If you look back at 1971, smokers and non-smokers alike were at the centers of social networks," says Fowler. "For people running companies and having parties, smoking was irrelevant. But during the '80s and '90s we saw a dramatic shift of smokers to the periphery of the social network. Contrary to what we might have thought in high school, smoking has become a supremely bad strategy for getting popular."

This marginalization of smokers appears to occur across all educational and economic demographics.

According to the researchers, this is an additional concern. Social marginalization leads to poor health. Smoking then is not only bad for your physical health but for your social health as well.

"What people need to understand is that because our lives are connected, our health is connected," says Christakis.

"Policy makers have an understandable tendency to treat people as atomized individuals, and to anticipate the impact of their policies accordingly," says Duncan Watts, professor of sociology at Columbia University, who was not involved with this study. "What this study-like the authors' previous study on obesity-points out clearly, however, is that individuals do not behave as atoms, but as part of a network. Although simple to state, the consequences of that observation are profound, and will require us to fundamentally rethink our intuition about the world."

"The culture of individualism is so strong that we sometimes forget how powerfully and silently social networks and those around us influence our health," said Richard Suzman, director of National Institute on Aging's Division of Behavioral and Social Research. "If decisions to quit cascade through social networks, then this study has provided public health campaigns a powerful new methodology with which to influence behaviors."

Written by David Cameron

http://hms.harvard.edu/

Tuesday, May 20, 2008

Structure of receptor for hot chili pepper and pain revealed

You can now not only feel the spicy kick of a jalapeno pepper, you can also see it in full 3D, thanks to researchers at Baylor College of Medicine in Houston.

Using sophisticated equipment, the research team led by Dr Theodore G. Wensel, professor of biochemistry and molecular biology at BCM, generated the first three dimensional view of the protein that allows you to sense the heat of a hot pepper. The report appears in the current issue of the Proceedings of the National Academy of Sciences.

"This protein, known as TRPV1, not only senses spicy foods, but also makes it possible to feel real heat and the pain and inflammation related to other medical conditions," said Wensel, senior author on the study. "This method of viewing the protein now gives us the chance to clearly see the functional relationship between outside stimuli and the nerve cell."

The outside stimulus used in this study was the heat of a chili pepper. It has been known for years that the burning sensation results from the action of a chemical known as capsaicin on TRPV1 found on the nerve cell membrane. TRPV1 is an ion channel, a tiny pore on the cell membrane that allows chemicals such as calcium to flux in and out.

"Any time you feel a burn or pain sensation, it is mediated by a TRPV1 channel. Different levels of heat are mediated by different TRP channels," said Dr. Vera Moiseenkova-Bell, a postdoctoral associate in Wensel's laboratory at BCM and first author of the study. "They are all related but each is regulated in a different manner."

Wensel said the three-dimensional image of TRPV1 revealed surprising information about its structure. It is made up of a pore domain embedded in the cell membrane, and a "hanging basket" of regulatory domains that extend into the interior of the cell.

"It's an unusual thing. There is a whole hollow 'basket' area but we don't know what's that's for," Wensel said. "Now the search is on to understand how the 'basket' area regulates the channel."

Isolating TRPV1 gives researchers an idea of how other channels are structured as well.

"Visualization of TRPV1 gives us insight on other TRP channels since they are structurally similar," said Moiseenkova-Bell. "Pharmaceutical companies target these TRP channels to make sure the drug binds properly. With this first structure we can start to build models of binding sites and hopefully in the future design more effective pharmaceuticals for a wide range of medical conditions."

Studying these channels is nothing new. In the past, scientists could measure the activity in the cells but it was unclear what each channel was responding to. Determining which proteins interacted with TRPV1, however, required Wensel's lab to create a purified model.

The protein had to be removed from cells, purified, and reconstituted in a synthetic membrane so researchers could control channel activity.

"Since calcium is involved in cell signaling, following the calcium movement confirmed the protein is active," said Wensel. "We are the first group to purify a TRPV1 channel and control what goes in and out when the channel opens."

http://www.bcm.edu

Dermatologists link family history to shingles susceptibility

Researchers at The University of Texas Medical School at Houston have identified family history as one reason why some people might be more susceptible to shingles, a severe skin condition. Their findings are published in the May 19 issue of Archives of Dermatology.

Shingles, or Herpes Zoster, is a burning, painful, itchy skin rash with blisters that can last up to five weeks and pain that can last months to years. Nearly 1 million shingles cases are diagnosed each year in the United States.

The more relatives you know of who have experienced an outbreak of shingles, the higher your risk, according to Stephen Tyring, M.D., Ph.D., clinical professor in the Department of Dermatology at the UT Medical School at Houston. "If just one blood relative has had shingles, you should get vaccinated. Your risk is double that of someone who has had no relatives with the virus. The estimate, however, is most valid for first degree relatives such as a mother, father or sibling."

Researchers at The Center for Clinical Studies, an outpatient clinic in Houston, examined 1,027 patients treated between 1992 and 2005. Of the more than 500 patients with shingles, 39 percent reported knowing of a blood relative who had suffered from shingles. In contrast, only 11 percent of age, sex, race-matched patients who had never had shingles knew of any blood relative who had shingles in the past.

Shingles is caused by the same virus that causes chickenpox, the varicella-zoster virus. Patients must have had chickenpox to get an outbreak of shingles. The virus is not eliminated from the body after an episode of chickenpox has ended.

"The virus lies dormant in your system until you have an accident, dental work, physical/emotional stress or your immune system is suppressed by a disease or virus. They can all be triggers that lead to a shingles outbreak," said Tyring, a co-author of the new study. Twenty percent of people who have had chickenpox will go on to have shingles.

People are less likely to get shingles if they have had the chickenpox vaccine, which was approved by the Food and Drug Administration in 1995.

Tyring, who was an investigator of the shingles vaccine, recommends the shingles vaccination for those with a family history. The shingles vaccine was approved for patients over 60 in 2006, and is now being studied in patients as young as 50 years of age.

In 25 to 50 percent of people older than 50, shingles pain can linger for months, or years, long after the rash and blisters have gone away - a condition called post-herpetic neuralgia.

http://www.uthouston.edu/

Monday, May 19, 2008

Too much water raises seizure risk in babies

It's a recurrent summer-time scenario in the pediatric emergency room and doctors from Johns Hopkins Children's are sounding the alarm on it: An otherwise healthy infant is brought in by panicked parents after suffering a seizure, which turns out to be caused by drinking too much water.

Pediatricians at Hopkins Children's see at least three or four such cases every summer, and while the seizures are benign and have no lasting effect on a child's health, they are quite dramatic and completely preventable, doctors say.

"Babies need extra fluids in the hot weather, but straight water is not one of them," says pediatrician Allen Walker, M.D., head of the Emergency Department at Hopkins Children's. "A parent's natural instinct is to give the baby water to prevent dehydration, but too much water can disrupt the delicate balance in a baby's body, leading to water intoxication. Before you know it, the baby is seizing."

Too much water dilutes sodium in the blood and flushes it out of the body, thus altering brain activity, which can lead to a seizure. Infants under 1 year of age may be more prone to these types of seizures than older children because a young infant's diet does not contain enough food sources to replenish the lost sodium. Also, an infant's immature kidneys cannot flush out excess water fast enough, causing a dangerous buildup of water in the body.

Breast milk and formula are the best way to keep a child under 1 year of age who is not eating solid foods hydrated, Walker says, and straight water should be avoided. Over-diluted formula can lead to water intoxication as well. Electrolyte-enriched pediatric drinks are not recommended for routine hydration.

Symptoms of water intoxication in an infant include:

  • changes in mental status, i.e., unusual irritability or drowsiness
  • low body temperature, usually 97 degrees or less
  • facial swelling or puffiness
  • seizures

Though any infant who consumes too much water can suffer water intoxication, the risk is highest among children who are already dehydrated, typically after a bout with viral or bacterial infections that cause vomiting and diarrhea. Symptoms of dehydration in a young child include dry mouth, increased thirst, irritability and reduced sweating and urination. An easy way to spot dehydration is if a child has fewer than three wet diapers in 24 hours, Walker says.

In otherwise healthy infants, water intoxication is one of the leading triggers of seizures. The most common type of childhood seizures are febrile seizures, occurring in 2 to 5 percent of all children under 5 years of age, according to the American College of Emergency Physicians.

http://www.hopkinschildrens.org

Friday, May 16, 2008

Heatwaves, floods and health concerns - special lecture on climate change and how we're dealing with it

Extreme floods, droughts and heatwaves, and how scientists are battling to deal with the effects of our rapidly warming planet, will be the subject of the first annual Grantham Lecture at Imperial College London on Thursday 22 May 2008.

Journalists are invited to the lecture, which will be given by Professor Sir Brian Hoskins, world-leading meteorologist and Director of Imperial's Grantham Institute for Climate Change.

Speaking at Imperial's South Kensington campus, Sir Brian will describe how global warming is affecting weather patterns, and how it could lead to extreme weather events such as scorching hot summers in Europe, and super-powered storms like Hurricane Katrina becoming more and more frequent.

During the lecture Sir Brian will outline the dramatic effects that climate change and extreme weather could have on the planet including: how rising temperatures are threatening to reduce biodiversity and damage important agricultural land; how rising sea levels could threaten the supply of fresh drinking water in some developing countries; and how changing temperatures could mean tropical diseases like malaria take hold in previously unaffected countries.

He will illustrate how researchers at Imperial College hope to tackle these problems, and how they are also working on alternative fuels and carbon capture technologies to reduce the levels of warming greenhouse gasses currently emitted into the atmosphere.

Speaking before the lecture, Sir Brian said: "When people talk about climate change, they often assume that changes will be slow and steady. However, some evidence suggests that as the climate changes, we will see extreme events, like the very hot British summer of 2003 and the contrasting summer floods in England in 2007, occurring more often.

"In my lecture, I'll look at the evidence for this, outline some of the consequences of volatile weather and climate change, and show what's being done here at Imperial to tackle these consequences."

Sir Brian's lecture, entitled, "Reflections on climate change and what we can do about it" takes place on Thursday 22 May 2008 from 18.30 - 19.30 in the Clore Lecture Theatre, Huxley Building, on Imperial's South Kensington campus.

Entry to this event is by ticket only. Free tickets must be reserved in advance by emailing amy.thompson@imperial.ac.uk

http://www.imperial.ac.uk

Obesity and unhealthy lifestyles linked to more complex urinary problems

People who are obese and lead unhealthy lifestyles are more likely to suffer from a larger number of urinary problems, according to a population-based study of more than 5,000 men and women published in the May issue of the UK-based urology journal BJU International.

According to the Boston Area Community Health Survey (BACH), other health issues that increase the risk of multiple lower urinary tract symptoms include diabetes, high blood pressure and heart disease. Women who have had hysterectomies and other gynaecological surgery also face an elevated risk, as do men who have undergone prostate or bladder surgery.

People who are older and have a lower social economic status are also more likely to experience complex problems.

The study, which received funding from the National Institute of Diabetes, Digestive and Kidney Diseases - part of the USA's National Institutes of Health - looked at the urological symptoms of 5,506 residents in Boston, Massachusetts. All were aged between 30 and 70 and 42 per cent were male. 34 per cent were white, 32 per cent were black and 34 per cent were Hispanic.

All the participants took part in detailed one-to-one interviews, which included urological symptoms, other medical conditions, physical characteristics such as weight and waist circumference, education, income and behavioural and psychosocial factors.

By carrying out a statistical analysis of the results, the researchers were able to group the participants with urological symptoms into distinct patterns or clusters, four for the women and five for the men. Using this method enabled the team to examine the relationship between complex urological problems and other health conditions or lifestyle factors.

"The cluster analysis method is highly objective and make no assumptions about which men or women are more likely to suffer from these common conditions" explains Dr Raymond C Rosen, Senior Scientist at the New England Research Institutes in Massachusetts.

"These results will hopefully aid our understanding of why urological problems occur and how we can manage these conditions more effectively".

Three-quarters of the women who took part in the survey reported at least one of the 14 urological symptoms included in the study.

Key findings included:

  • Four female clusters were identified.
  • The majority of the women who reported symptoms (54 per cent) fell into Cluster One which was characterised by storage problems, such as needing to go to the toilet frequently and getting up to go during the night. They had fewer overall symptoms than the women in the other clusters.
  • Symptoms increased in number and severity until they reached Cluster Four, where women had the highest number of urological symptoms. Eight per cent of women fell into this cluster.
  • The women who experienced symptoms had a higher Body Mass Index than the women who didn't and this peaked in Cluster Four, where the average BMI was 34.5 and just under 65 per cent were obese.
  • Women in Cluster Four were four times more likely to suffer from diabetes than women who reported no urological symptoms.
  • On average, symptomatic women were older than women who didn't report any symptoms and average ages in the more symptomatic clusters were higher.
  • A woman's social economic status was much more likely to predict her level of urology symptoms then her race. For example, women in Cluster Four were more likely have a low social economic status.

Just over two-thirds of the men who took part in the study (69 per cent) reported urological symptoms.

Key findings included:

  • Five male clusters were identified.
  • Half of the men were assigned to Cluster One, which covered storage problems and included the male participants with the fewest number of symptoms. The number of symptoms increased in Clusters Two, Three and Four.
  • Eight per cent of the symptomatic men fell into the highest category, Cluster Five, with an average of 10 symptoms per person.
  • There was a significant increase in age across the groups - the average age of the men with no symptoms was 44, compared with 59 in Cluster Five.
  • The researchers also noticed significant racial differences. Cluster Four had the lowest percentage of black and Hispanic men and Hispanic men were also under-represented in Cluster Five.
  • 40 per cent of the men in Cluster Five came from the lowest social economic status group.
  • Men were much more likely to find themselves in Cluster Five if they had a sedentary lifestyle, with 54 per cent recording the lowest levels of physical activity, compared with 20 per cent for men with no symptoms.
  • Men in Clusters Three to Five reported significantly higher levels of diabetes, blood pressure and heart problems. For example, 40 per cent of men in Cluster Five reported problems with cardiovascular disease, compared with less then 20 per cent in Cluster One.
  • 43 per cent of the men in Cluster Five were medically obese.
  • There were no significant differences in smoking or alcohol consumption across the clusters, apart from the fact that Cluster Five contained a higher percentage of men who didn't drink (41 per cent). 26 per cent of men with no symptoms abstained, as did 25 to 30 per cent of the men in the other clusters.

"The findings of the BACH survey are very useful for clinicians and health promotion experts as they provide evidence of a wide range of factors that influence lower urinary tract symptoms, such as age, other illnesses, lifestyle, economic status and race" says Dr Rosen.

"They underline the importance of clinicians carrying out a thorough urological assessment of patients who fall into these high risk groups."

"And they also provide a useful basis for future research into this highly complex area."

The BACH Survey was carried out by investigators from the New England Research Institutes, led by Dr John B McKinlay. Their findings are summarised in two papers in BJU International - on the male and female studies - written in collaboration with urology experts from Cornell University in New York and the University of Texas and medical researchers from Pfizer Inc.

http://www.bjui.org

Thursday, May 15, 2008

Regenerative medicine offers hope in spinal cord injury

Spinal cord injury (SCI) can be a catastrophic event for the individual. Traditionally, such injuries were viewed as permanent, irreversible neurological dysfunction, but over time research has shown some neuroplastic capability of the injured adult mammalian spinal cord. However, spontaneous functional recovery post-SCI is very modest.

The peripheral nervous system (PNS), in contrast, is more robust in its capacity to regenerate following damage. Among the strategies to utilize elements of the PNS for regeneration of spinal cord, neurotization - the rerouting of intact peripheral nerves originating from spinal segments above the site of injury - has previously been studied and even applied clinically. Functional improvements after spinal cord injury (SCI) have been reported anecdotally following neurotization, but the underlying mechanisms have been poorly understood.

Using a rat model for spinal cord injury, Scientists at Harvard have shown significant functional recovery in neurotized animals versus controls. In addition to limited reinnervation in the target muscles, neurotized animals demonstrated multiparameters of neural reorganization in the distal lumbar cord. The findings are published in the May issue of Regenerative Medicine1 published by Future Medicine.

Dr Yang D. Teng, Director of the Laboratories of Spinal Cord injury and Neural Stem Cell Research at Harvard University together with colleagues from the USA, Turkey and Puerto Rico, hypothesized that neurotization-mediated recovery is primarily attributable to CNS neuroplasticity that therefore manifests optimal response during particular therapeutic windows. To test this hypothesis in the rat, they anastomosed the T12 intercostal nerve to the ipsilateral L3 nerve root 1-4 weeks after T13-L1 midline hemisection. Neurobehavioral function, as assessed by locomotion, extensor postural thrust and sciatic functional index of SCI rats receiving neurotization 7-10 days postinjury, recovered to levels close to non-SCI controls with neurotization only, beginning 3-5 weeks postanastomosis. Conversely, hindlimb deficits were unchanged in hemisected controls with sham neurotization or 4 weeks-delayed neurotization, and in rats that had undergone T13-L1 transection plus bilateral anastomoses.

In addition to limited reinnervation in the target muscles, neurotized SCI animals demonstrated multiparameters of neural reorganization in the distal lumbar cord, including enhanced proliferation of endogenous neural stem cells, increased immunoreactivity of serotonin and synaptophysin, and neurite growth/sprouting, suggesting that anastomosing functional nerves with the nerve stump emerging distal to the hemisection may help re-establish locomotor pattern generation in the dysfunctional spinal cord. This conclusion was validated by the fact that severance of the T13-contralateral cord abolished the postanastomosis functional recovery.

While the goal of reclaiming neural control of a denervated organ via neurotization should be further explored, the authors suggest that this procedure could be utilized for the purpose of enhancing neuroplasticity and activating the inherent regenerative and repair potential of the spinal cord. This approach may have additional synergistic potential when combined with other treatment strategies that also aim at inducing neuroplasticity in the injured spinal cord. Task-specific physical activities (e.g., locomotor training), electrical stimulation and NSC transplantation, for example, may be employed in conjunction with the surgical procedure to provide additional augmentation of the plastic potential of the spinal cord and facilitate reorganization of neural circuitry to achieve greater functional and anatomical improvement.

http://www.futuremedicine.com

Wednesday, May 14, 2008

Chronic disease management: Does it improve health and save money?

A study published in the May/June issue of Health Affairs reports on the first randomized trial providing a scientifically valid look at what one might expect from chronic disease management programs that serve low-income individuals. The study result provides good news for state Medicaid leaders struggling to meet the needs of individuals with chronic conditions and also suggests that some disease management efforts, even among relatively low-risk patients, may be an effective strategy.

While chronic disease management programs, also known as chronic care management, have become widespread across the United States, gaining favor with employer groups, health-care organizations and health payers, these programs are being increasingly questioned because very little scientific evidence exists regarding their effectiveness and fiscal impact.

Researchers from the Indiana University School of Medicine, the Regenstrief Institute, and the School of Public and Environmental Affairs at Indiana University-Purdue University Indianapolis designed a study to determine whether chronic disease management of individuals with diabetes and/or congestive heart failure (CHF) improves health outcome and lowers healthcare costs.

In contrast to earlier studies, the researchers randomly assigned individuals with the two chronic conditions to either chronic disease management or a control group based on their primary care provider's location. The researchers used a predictive model to identify individuals at risk for high levels of future health-care utilization. Individuals judged to be at highest risk were given intensive health care management conducted by a nurse care manager. Those with lower risk were provided with education and care support over the phone. Their findings were much more complex than they had anticipated.

"The telephonic support, when given to the lower risk group for either disease, resulted in a significant reduction in subsequent health-care claims paid," said study senior author Thomas S. Inui, M.D., IU School of Medicine associate dean for health care research and Sam Regenstrief Professor of Health Services Research. Dr. Inui also is president and CEO of the Regenstrief Institute.

Results for high-risk patients were more ambiguous. The researchers found that nurse care management resulted in lower average claims for high-risk CHF patients, but slightly higher average claims for high-risk diabetes patients, although neither effect was found to be statistically significant.

One of the strengths of this evaluation is that the fiscal impact analysis included the costs of delivering the chronic disease management intervention, not just the impact on claims for subsequent utilization. "Once we considered these additional costs, we discovered the net fiscal impact of chronic disease management was positive only for low-risk CHF patients," said lead author Ann M. Holmes, Ph.D., associate professor, IUPUI School of Public and Environmental Affairs.

http://www.iupui.edu

Tuesday, May 13, 2008

How your heart sounds could tell your heart attack risk

According to scientists in the United States, a doctor may be able to determine a person's risk of having a heart attack just by listening to their heart with a stethoscope.

The scientists from Walter Reed Army Medical Center in Washington say that a certain noise is made by the heart when fatty deposits on the wall of the arteries accumulate and this can be heard with a stethoscope.

This sound which is caused by the build up of arterial plaque is called a carotid bruit and is the sound that blood makes when it passes over an obstruction in the carotid artery, the main channel for supplying blood to the head and neck.

The researchers analyzed 22 studies featuring 17,295 heart patients who were followed up for four years and they found that the presence of a carotid bruit was linked to double the risk of suffering a heart attack compared to those without a bruit and such people were 2.5 times more likely to die because of a heart attack.

Until now carotid bruits have usually been associated with bleeding in the brain.

Dr. Christopher Pickett and colleagues say their research shows that the presence of a carotid bruit significantly increases the likelihood of cardiovascular death or heart attack.

The researchers say if doctors can determine that a patient has a carotid bruit, they may be able to design preventative therapies to help reduce heart attack risks.

Study shows how T cell's machinery dials down autoimmunity

A St. Jude Children's Research Hospital study shows that T cells, the body's master immune regulators, do not use simple on/off switches to govern the cellular machinery that regulates their development and function. Rather, they possess sophisticated molecular controls that enable them to adjust their function with exquisite precision. Such subtle adjustment enables T cells to modulate their development and function, including avoiding autoimmunity.

In autoimmune disease, rather than attacking invading microbes, the immune system attacks the body's own organs, tissues or cells. Some 80 autoimmune diseases are known, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis and lupus.

"Among the many mysteries surrounding autoimmune diseases is why they can sometimes take decades to manifest themselves," said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology. "Our findings hint that this delayed onset could be explained by subtle defects in the molecular controls on T cells." Such T cells are white blood cells whose duties include shutting down the immune system when it has done its job and suppressing T cells that can attack the body.

Vignali is the senior author of a report on this work that appears in the advance online publication of the journal "Nature Immunology."

The researchers explored the function of T cell receptors, proteins that span the cell membrane of T cells. These receptors receive outside signals that instruct T cells to develop, proliferate and transmit those signals into the cell. The St. Jude investigators sought to understand why T cell receptors need many copies of switch-like components called immunoreceptor tyrosine-based activation motifs (ITAMS). ITAMs are components of the CD3 adaptor proteins that attach to the T cell receptor and help transmit the control signals from the T cell receptor into the cell.

"The ITAMs we studied are little molecular tags inside the cell by which the T cell receptor communicates to the rest of the cell," Vignali said. "The mystery we wanted to address was why the T cell receptor needs 10 ITAMs to do its job. Why not just have a simple on/off switch?"

To explore the role of multiple ITAMs, Jeff Holst, Ph.D., the paper's first author and a St. Jude postdoctoral scientist, used a technique developed in the Vignali lab to produce mice whose T cells have variations in the number and type of functional ITAMs. The technique involved using a virus as a genetic cargo-carrier to transport genes for different combinations of normal and mutant non-functional ITAMs into the mouse cells.

The researchers found that reducing the number of normal ITAMs caused the mice to develop autoimmune disease. However, the investigators also found that some mice with fewer than normal functional ITAMs did not become sick with autoimmune disease. Vignali said this finding suggests that it is not just the number of ITAMs, but also their type that may influence T cell function.

"We theorized that there were two possibilities why the immune system needs so many ITAMs," he said. "One is that the requirement was purely quantitative, and that the ITAMs were there for signal amplification. The second possibility is that different ITAMs do slightly different things-they do have slightly different structures, so maybe they bind to some signaling molecules better than others; and their positions in the T cell receptor are different. So, while our primary observation is that quantity is more important than ITAM type, we also found that type has some influence."

The researchers' analyses of the immune systems of the altered mice indicated that reducing the number of normal ITAMs crippled a process called "negative selection." In this process, the immune system rids itself of immature T cells that might attack the body's own cells, causing autoimmune disease. Vignali said that these findings might provide insight into how autoimmune diseases start.

"One implication of our findings is that a relatively small defect in the efficiency of signal transduction through the T cell receptor could give rise to a subtle failing in negative selection, which gives rise over a long period of time to a few overly active T cells that might initiate autoimmunity," Vignali said. "Clearly from our studies there is the possibility that you don't really need a very big reduction in T cell receptor signal strength to have a defect in negative selection."

The study also showed that different T cell functions required different numbers of functional ITAMs. "We were surprised to find that many ITAMs were required to make T cells divide and expand, but only one or two was required to make T cells secrete cytokines," Vignali said. Cytokines are soluble proteins used by cells of the immune system to communicate and send messages to one another. Vignali said these basic findings represent only the beginning of more detailed studies of the role of ITAMs in T cell function.

"We believe this idea that T cell signaling acts more like a rheostat than an on/off switch offers significant new insights into how T cell development and function is controlled," Vignali said.

http://www.stjude.org/

Monday, May 12, 2008

Australian scientists warn, to avoid cancer keep alcohol to a minimum

Australian scientists are warning that alcohol can increase the risk for a number of cancers.

Research conducted by scientists at the Cancer Institute has revealed that drinking two units of alcohol on a daily basis significantly increases the risks of developing breast, bowel, throat and mouth cancer.

The researchers say alcohol raises the risk of breast cancer by 22 per cent, the risk of cancer of the oesophagus by 50 per cent, cancer of the larynx by 40 per cent and the risk of mouth cancer by up to 75 per cent, and men who drink four units of alcohol a day increase their risk of bowel cancer by 64 per cent.

These revelations contrast starkly to a plethora of earlier research which has found that moderate amounts of red wine could have health benefits and may help to prevent heart disease and strokes.

The Cancer Institute says that the health benefits of alcohol consumption may have overestimated and most evidence suggests that one drink every two days may be cardioprotective, but only in men over 45 years of age and women after menopause.

They say there is no evidence to support the theory that people should take up or maintain drinking alcohol for their health.

The report by the Cancer Institute of New South Wales, found in fact there is no safe level of alcohol and alcohol consumption should be kept to an absolute minimum.

According to Professor Jim Bishop from the Cancer Institute, that alcohol is a carcinogen and known to increase the risk of several cancers, is well established and he says even drinking moderate levels of alcohol on a regular basis can increase the risk.

Professor Bishop says as far as cancer is concerned no benefit is derived from alcohol.

The research is based on data from an international audit of recent cancer research which found that cancer is on the increase.

The researchers say although alcohol is widely available and widely consumed, it is also a known risk factor for several cancers and is classified by the World Health Organisation (WHO) as a Group 1 carcinogen - the highest classification available and signifies the cancer risk for humans.

According to the report 70% of adults in NSW drink alcohol, which comes second only to tobacco as a preventable cause of drug-related deaths - people who smoke and drink are at a far greater risk.

The report says in 2003 there were an estimated 2,844 new cases of cancer and 1,358 deaths from cancer in Australia were attributed to excessive alcohol consumption.

Assistant Health Minister Verity Firth says people need to reconsider their alcohol intake and make the same sorts of decisions about alcohol as they do about other habits such as smoking.

The researchers are calling for tougher drinking guidelines.

The Cancer Institute NSW was founded in July 2003 and is Australia's first State-wide Government cancer control agency which is responsible for reducing cancer incidence, increasing cancer survival, improving the quality of life for cancer patients and their carers and providing expert advice on cancer.

Human aging gene found in flies

Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have found a fast and effective way to investigate important aspects of human ageing.

Working at the University of Oxford and The Open University, Dr Lynne Cox and Dr Robert Saunders have discovered a gene in fruit flies that means flies can now be used to study the effects ageing has on DNA. In new work published today in the journal Aging Cell, the researchers demonstrate the value of this model in helping us to understand the ageing process. This exciting study demonstrates that fruit flies can be used to study critical aspects of human ageing at cellular, genetic and biochemical levels.

Dr Lynne Cox from the University of Oxford said: "We study a premature human ageing disease called Werner syndrome to help us understand normal ageing. The key to this disease is that changes in a single gene (called WRN) mean that patients age very quickly. Scientists have made great progress in working out what this gene does in the test tube, but until now we haven't been able to investigate the gene to look at its effect on development and the whole body. By working on this gene in fruit flies, we can model human ageing in a powerful experimental system."

Dr Robert Saunders from The Open University added: "This work shows for the first time that we can use the short-lived fruit fly to investigate the function of an important human ageing gene. We have opened up the exciting possibility of using this model system to analyse the way that such genes work in a whole organism, not just in single cells."

Dr Saunders, Dr Cox and colleagues have identified the fruit fly equivalent of the key human ageing gene known as WRN. They find that flies with damage to this gene share important features with people suffering from the rapid ageing condition Werner syndrome, who also have damage to the WRN gene. In particular, the DNA, or genetic blueprint, is unstable in the flies that have the damaged version of the gene and the chromosomes are often altered. The researchers show that the fly's DNA becomes rearranged, with genes being swapped between chromosomes. In patients with Werner syndrome, this genome instability leads to cancer. Cells derived from Werner syndrome patients are extremely sensitive to a drug often used to treat cancers: the researchers show that the flies that have the damaged gene are killed by even very low doses of the drug.

Professor Nigel Brown, Director of Science and Technology, Biotechnology and Biological Sciences Research Council said: "The ageing population presents a major research challenge to the UK and we need effort to understand normal ageing and the characteristics that accompany it."

"Fruit flies are already used as a model for the genetics behind mechanisms that underlie normal functioning of the human body and it is great news that this powerful research tool can be applied to such an important area of study into human health."

http://www.bbsrc.ac.uk/

How your heart sounds could tell your heart attack risk

According to scientists in the United States, a doctor may be able to determine a person's risk of having a heart attack just by listening to their heart with a stethoscope.

The scientists from Walter Reed Army Medical Center in Washington say that a certain noise is made by the heart when fatty deposits on the wall of the arteries accumulate and this can be heard with a stethoscope.

This sound which is caused by the build up of arterial plaque is called a carotid bruit and is the sound that blood makes when it passes over an obstruction in the carotid artery, the main channel for supplying blood to the head and neck.

The researchers analyzed 22 studies featuring 17,295 heart patients who were followed up for four years and they found that the presence of a carotid bruit was linked to double the risk of suffering a heart attack compared to those without a bruit and such people were 2.5 times more likely to die because of a heart attack.

Until now carotid bruits have usually been associated with bleeding in the brain.

Dr. Christopher Pickett and colleagues say their research shows that the presence of a carotid bruit significantly increases the likelihood of cardiovascular death or heart attack.

The researchers say if doctors can determine that a patient has a carotid bruit, they may be able to design preventative therapies to help reduce heart attack risks.

Thursday, May 8, 2008

Nitrates in vegetables protect against gastric ulcers

Vegetables that are rich in nitrates protect the stomach from damage. This takes place through conversion of nitrates into nitrites by the bacteria in the oral cavity and subsequent transformation into biologically active nitric oxide in the stomach. The Swedish researcher Joel Petersson has described the process, which also means that antibacterial mouthwashes can be harmful for the stomach.

"Nitrates in food have long been erroneously linked to an increased risk of cancer," says Joel Petersson of Uppsala University's Department of Medical Cell Biology.

He instead thinks that nitrate-rich vegetables such as spinach, lettuce, radishes and beetroot have a positive affect on the stomach by activating the mucous membranes' own protective mechanisms, thus reducing the risk of problems such as gastric ulcers.

In the body the blood circulation transports nitrates to the salivary glands, where they are concentrated. When we have eaten nitrate-rich food our saliva thus contains large amounts of nitrates, which the bacteria of the oral cavity partially convert into nitrites. When we swallow the nitrites they come into contact with acid gastric juice, and are then converted into the biologically active substance nitric oxide. This results in our developing high levels of nitric oxide in the stomach after eating vegetables.

It has long been known that nitric oxide is produced by various enzymes in the human body, but the fact that nitric oxide can also be formed in the stomach from nitrites in the saliva, entirely without the involvement of enzymes, is a relatively new discovery. Researchers still have very little idea of how the stomach is affected by these high levels of nitric oxide. Joel Petersson's thesis shows that the nitric oxide that is formed in the stomach stimulates the protective mechanisms of the mucous membrane - because the stomach constantly has to protect itself so as not to be broken down together with the food ingested. Two such important defence mechanisms are the stomach's constant renewal of the mucous layer that covers the mucous membrane and its maintenance of a stable blood flow in the mucous membrane. The nitric oxide widens the blood vessels in the mucous membrane, thus increasing the blood flow and regulating elimination of the important mucus. Together, these factors lead to a more resistant mucous membrane.

Using animal models Joel Petersson and his colleagues have shown that nitrate additives in food protect against both gastric ulcers and the minor damage that often occurs in the gastrointestinal tract as a result of ingestion of anti-inflammatory drugs.

"These sorts of drugs are very common in the event of pain and inflammation. They have the major disadvantage of causing a large number of serious side effects in the form of bleeding and ulcers in the gastrointestinal tract. With the aid of a nitrate-rich diet you can thus avoid such damage," he explains.

The thesis also shows that the bacteria in the oral cavity are very important to the process of nitrates in food protecting the stomach's mucous membrane. This has been examined in that rats have been given nitrate-rich feed, whereby some of them have also simultaneously received an antibacterial oral spray. When these rats were then given anti inflammatory drugs, damage to the mucous membrane only occurred in the ones that had received the oral spray. In the latter the nitrates no longer had a protective effect on the mucous membrane, as the oral spray had killed the important bacteria that normally convert nitrates into nitrites.

"This shows how important our oral flora is. The fact that these bacteria are not just involved in our oral hygiene but also play an important role in the normal functions of the gastrointestinal tract is not entirely new. It is currently an important issue, as antibacterial mouthwashes have become more and more common. If a mouthwash eliminates the bacterial flora in the mouth this may be important to the normal functioning of the stomach, as the protective levels of nitric oxide greatly decrease," says Joel Petersson.

In his opinion the research results also provide a new approach to the importance of fruit and vegetables in our diet.

"If we followed the National Swedish Food Administration's recommendation and ate 500 g of fruit and vegetables per person per day it would definitely be better for our stomachs.

Joel Petersson's thesis is being scrutinised at Uppsala University on 9 May.

http://publications.uu.se/

Wednesday, May 7, 2008

New laser treatment for vocal-cord cancer

An innovative laser treatment for early vocal-cord cancer, developed at Massachusetts General Hospital (MGH), successfully restores patients' voices without radiotherapy or traditional surgery, which can permanently damage vocal quality.

This new option for patients, which has now been used in more than 25 patients, was reported on May 1 at the annual meeting of the American Broncho-Esophagological Association, and the data will soon be published as a supplement to the Annals of Otology, Rhinology, & Laryngology.

"We had previously adapted lasers that target blood vessels to treat precancerous vocal-cord dysplasia and a variety of benign vascular lesions. We have now applied that experience to treat vocal-cord cancer, which is diagnosed in several thousand American patients each year," says Steven Zeitels, MD, director of the MGH Voice Center.

Zeitels' team began applying pulsed lasers to the treatment of early vocal-cord cancer more than five years ago. After successfully treating the first eight patients with the pulsed-dye laser, Zeitels' group switched to the more precise pulsed Potassium-Titanyl-Phosphate (KTP) laser, which is even less likely to damage delicate vocal-cord tissue. The use of specific wavelengths of laser light to target blood vessels was originally applied to the removal of vascular skin lesions like port-wine stains by Rox Anderson, MD, now director of the MGH Wellman Center of Photomedicine. In a close collaboration with Anderson, Zeitels previously developed application of these angiolytic lasers to benign and precancerous vocal-cord lesions.

As Zeitels reported at the ABEA meeting, the first 22 patients receiving pulsed laser treatment for vocal-cord cancer are cancer-free up to 5 years after treatment, without removal of vocal-cord tissue or loss of voice quality. Some have required second or third laser treatments to remove residual disease, but another benefit of the therapy is that it does not rule out future therapeutic options. Zeitels notes that this treatment has become a standard management approach at MGH and should soon spread to other institutions in the US and abroad. He estimates that 90 percent of patients with early vocal-cord cancer would be candidates for pulsed-KTP laser treatment.

"Currently the optimal angiolytic laser for vocal-cord problems, the pulsed-KTP laser is a critical innovation in the instrumentation arsenal of the laryngeal surgeon," says Zeitels. "It has greatly enhanced the precision by which we can perform many procedures for chronic laryngeal diseases, both in the operating room, accompanied by the surgical microscope, and in the office." Zeitels is the Eugene B. Casey Professor of Laryngeal Surgery at Harvard Medical School (HMS).

The MGH Voice Center team has created a number of groundbreaking procedures and was the first in the world to treat vocal cords and other structures in the larynx with controlled pulses of the green KTP laser light. Zeitels has been recognized for his 2006 use of pulsed-KTP laser to treat Steven Tyler of the rock band Aerosmith for vocal-cord hemorrhage. With his unique perspective on voice restoration and preservation resulting from years of treating elite singers, Zeitels was called on to work with Julie Andrews after she lost her singing voice due to a failed surgical procedure. He subsequently has collaborated with Miss Andrews to increase awareness of voice problems and spearhead a research project investigating new voice restoration surgical procedures.

The MGH and HMS instituted one of the first academic programs in Laryngology in the United States in 1870. The MGH program was discontinued in the 1920s and was reestablished in 2004 with the philanthropic assistance of the Eugene B. Casey Foundation and the Institute of Laryngology and Voice Restoration (ILVR - website at http://ilvr.org/), a patient-based organization with the mission to further research, clinical care and education in laryngeal and voice disorders. Miss Andrews is the honorary chairwoman of the ILVR, and the organization's president is John Ward, PhD, a Northwestern University professor who was the first patient to receive the new laser treatment for vocal-cord cancer.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare HealthCare System, a Boston-based integrated health care delivery system.

http://www.mgh.harvard.edu/

New understanding of how a mole develops into melanoma

Researchers have discovered how a mole develops into melanoma by showing the interaction of two key proteins involved in 60-70 percent of tumors. The Penn State scientists also demonstrate that therapeutic targeting of these proteins is necessary for drugs to effectively treat this deadly form of cancer.

"We have shown that when two proteins - (V600E)B-Raf and Akt3 - communicate with one another in a mole, they cooperate leading to the development of melanoma," said Gavin Robertson, lead author and associate professor of pharmacology, pathology and dermatology, and director of the Foreman Foundation Melanoma Therapeutics Program at the Penn State College of Medicine Cancer Institute. "We have also shown that effective therapies for melanoma need to target both these proteins, which essentially eliminates the tumors."

Melanoma is the most deadly form of skin cancer because it metastasizes or moves around the body so quickly. In general, people with advanced-stage disease only have months to live. Currently, melanoma kills one person every hour in the U.S., and is predicted to affect one in 50 people by 2010. In recent years, researchers have zeroed in on two key genes - B-Raf and Akt3 - that cause this deadly cancer, and which could be important targets in the treatment of melanoma.

B-Raf is the most mutated gene in melanoma. The mutant protein, (V600E)B-Raf, produced by this gene is important in helping mole cells survive and grow but it is unable to form melanomas on its own. Nearly 90 percent of all moles have the mutant protein but it is not fully clear why only some of them turn into melanomas.

Robertson and his colleagues have found that a second protein - produced by Akt3 - regulates the activity of the mutated B-Raf, which aids the development of melanoma.

"What we have found is a second event that is necessary for melanomas to develop," added Robertson, whose findings are reported in the May 1 issue of the journal Cancer Research.

While comparing proteins within normal moles and human melanoma cells, the Penn State researchers noticed that the two proteins were communicating with one another only among melanoma cells but not among normal cells.

When the Akt3 protein was put into cells in conjunction with the mutant B-Raf gene, they were better able to form melanomas compared to cells just containing the mutant B-Raf gene.

"This tells us that you can have a mole but it cannot turn into melanoma without the presence of the Akt3 protein," explained Robertson.

While it is still unclear what brings the B-Raf and Akt3 proteins together, the Penn State researchers say they now have a better understanding of how these two proteins interact to cause melanoma.

The initial mutation of the B-Raf gene helps to create moles, but high levels of B-Raf activity due to the mutation prevents the cells from becoming a melanoma. It is only when the Akt3 protein is present in those cells and communicates with B-Raf that it lower its activity, thereby creating favorable conditions within the mole for cells to multiply, and allow them to turn into a melanoma.

Robertson said the discovery could pave the way for newer and more effective treatments for melanoma.

"We have shown that if we target the two proteins separately, it somewhat inhibits the development of tumors but if we target them together, the development of tumors gets inhibited significantly," he added. "It validates these proteins as key targets for effective melanoma therapy."

Robertson envisions that future physicians could look at blood samples from melanoma patients containing melanoma cells and determine whether the two proteins are in their cells. The patients could then receive drugs that target these proteins to more effectively treat their disease. It would be personalized cancer treatment that would be more effective and less toxic with fewer side effects, the Penn State researcher explained.

"In the search for a cure for melanoma, we are now closer because we know that we need to target these two proteins in order to have a dramatic impact on the development of melanoma," Robertson added.

For patients, this means that in the future, some new drug could target these proteins to treat advanced disease or be added to sunscreen lotion, for instance, that would prevent Akt3 functioning in the cell. It would not only help control a tumor, but also prevent one as well.

http://www.psu.edu/

Blocked brain enzyme shows potential as target for appetite control, weight loss and blood sugar management

Imagine being able to tone down appetite and promote weight loss, while improving the body's ability to handle blood sugar levels.

That's just what Tony Means, PhD, and his team at the Duke University Medical Center were able to do when they blocked a brain enzyme, CaMKK2, in mice.

"We believe we have identified an important drug development target that could potentially turn into a metabolic triple play: appetite control, weight loss and blood sugar management," said Means, who is the Nanaline H. Duke Professor and Chairman of Pharmacology and Cancer Biology.

For many years, scientists have been identifying and testing every step of the appetite stimulation and suppression pathways in search of a target. Such research is considered critical to finding ways for people to better control their weight and minimize their risk of developing diabetes, heart disease and other health conditions.

Activation of the enzyme CaMKK2 is just one step in the appetite stimulation pathway located in the hypothalamus section of the brain. An empty stomach releases the hormone ghrelin, which launches a cascade of signals that ultimately results in increased appetite.

Means and colleagues believed that CaMKK2 in the ghrelin pathway might be a likely candidate for study, because it activates AMPK, an enzyme that stimulates animals to eat and gain weight. They tested their theory in several ways, the results of which are published in the May issue of Cell Metabolism. The work was funded by NIH grants, as well as by the Australian Research Council, National Heart Foundation, and the National Health and Medical Research Council of Australia.

First they blocked CaMKK2 in mice with a specialized molecule inhibitor and then measured food intake. These mice ate significantly less food than untreated mice during the six days in which they were evaluated, and also lost body weight, which led the scientists to think they might be on to something.

Next they studied a group of mice that normally do not make CaMKK2 and found that the molecule inhibitor did not change feeding behavior or reduce weight. "The fact that blocking CaMKK2 worked in normal mice to make them eat less and lose weight, but not in mice missing the enzyme, provides compelling evidence that CaMKK2 signaling is a requirement for appetite control," Means said.

They also studied both normal mice and mice missing CaMKK2 to learn how these types responded to low-fat and high-fat diets. After nearly 30 weeks on the specific diets, the normal mice on the high-fat diet became diabetic - they were unable to respond to insulin and weren't able to manage blood sugar levels well. In contrast, the normal mice on a low-fat diet stayed healthy.

In mice missing CaMKK2, the scientists found that they stayed healthy regardless of whether they were on a low-fat or high-fat diet. The CAMKK2-negative mice apparently were protected from changes that lead to diabetes in a high-fat diet.

"Remarkably, we find that blocking CaMKK2 in the brain prevents the deposits of fat in liver and skeletal muscle that are characteristic of obese, diabetic patients," Means said. "We find this very exciting and are trying to understand the mechanism responsible for this protective effect, as well as to identify more potent drugs to inhibit CaMKK2."

http://medschool.duke.edu/

Tuesday, May 6, 2008

Computer keyboard five times filthier than the toilet seat!

According to scientists in Britain your computer keyboard could contain a virus which threatens more than just what is on the screen - they say it poses a considerable health risk which equates to those presented by a toilet seat.

The consumer-advocacy group, in Britain, 'Which?' commissioned a microbiologist to test just how clean the average computer keyboard was by looking at more than thirty keyboards in its own offices.

The results were then compared to those found on toilet seats and a toilet door handles.

The outcome was quite shocking in that one keyboard had to be removed from the office as it was revealed to be five times filthier than the toilet seat.

The keyboard apparently harboured 150 times over the level of acceptable bacteria and two other keyboards were found to contain Staphylococcus aureus, which can cause skin infections and food poisoning.

While the revelation might make most wonder at the exact circumstances under which the keyboards were being used, the fact remains that few users consider the cleanliness of their keyboard and the dirt which builds up over time.

The research also involved a survey on how often people cleaned their keyboards along with washing their hands after trips to the bathroom.

These results revealed that 11 percent never cleaned their keyboards, 46 percent cleaned them less than once a month and only 29 percent cleaned their keyboards regularly.

The microbiologist, James Francis from Kingmoor Technological Services in Carlisle, suggests the lack of proper lunch breaks is responsible for the contamination and says more and more people are eating at their desks and are transferring food from hand to mouth.

Dr. Francis says this exacerbates the problem which is also found with telephones where many pathogenic disease-causing bacteria are also found.

He says this is the case particularly on telephones in hotel rooms and as a rule if equipment appears dirty, common sense says there is a good chance it carries bacteria.

Experts say the results are not surprising as most bacteria are transmitted by hand contact.

In the States earlier this year the Centers for Disease Control and Transmission reported that a virus spread through a primary school in Washington was likely to have been spread by dirty computer keyboards - at least one classroom keyboard tested positive for flu germs.

The CDC says this was the first time the spread of flu germs had been linked to computer equipment and it is possible computers play a bigger role in the spread of germs than was previously suspected.

Computer users are urged to regularly unplug their computers, turn the keyboards upside down and shake them so food fragments and whatever else has accumulated there is removed and to use alcohol wipes to really get rid of bacteria.

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