UCLA researchers develop biomarker for rapid relief of major depression: Brain-wave patterns may predict how effective medication will be

It is a long, slow slog to treat major depression. Many antidepressant medications are available, but no single biomarker or diagnostic test exists to predict which one is right for an individual. As a result, for more than half of all patients, the first drug prescribed doesn't work, and it can take months to figure out what does.

Now, based on the final results of a nationwide study led by UCLA, clinicians may be able to accurately predict within a week whether a particular drug will be effective by using a non-invasive test that takes less than 15 minutes to administer. The test will allow physicians to quickly switch patients to a more effective treatment, if necessary.

The study, called the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression, or BRITE-MD, measured changes in brain-wave patterns using quantitative electroencephalography (QEEG), a non-invasive, computerized measurement that recognizes specific alterations in brain-wave activity. These changes precede improvement in mood by many weeks and appear to serve as a biomarker that accurately predicts how effective a given medication will be. The study results appear in two articles published in the September issue of the journal Psychiatry Research.

Nine sites around the country collaborated on the study, which enrolled a total of 375 people who had been diagnosed with major depressive disorder (MDD). Each individual was given a baseline QEEG at the beginning of the trial and then prescribed the antidepressant escitalopram, commonly known as Lexapro, one of a class of drugs known as selective serotonin re-uptake inhibitors that are commonly prescribed for depression. After one week, a second QEEG was taken. The researchers examined a biomarker called the antidepressant treatment response (ATR) index — a specific change in brain-wave patterns from the baseline QEEG.

Subjects were then randomly assigned to continue with escitalopram or were given a different drug. A total of 73 patients who remained on escitalopram were tracked for 49 days to see if their results matched the prediction of the ATR biomarker. The ATR predicted both response and remission with an accuracy rate of 74 percent, much higher than any other method available. The researchers also found that they could predict whether subjects were more likely to respond to a different antidepressant, bupropion, also known as Wellbutrin XL.

"Until now, other than waiting, there has been no reliable method for predicting whether a medication would lead to a good response or remission," said Dr. Andrew Leuchter, professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and lead author of the study. "And that wait can be as long as 14 weeks. So these are very exciting findings for the patient suffering from depression. The BRITE results are a milestone in our efforts to develop clinically useful biomarkers for predicting treatment response in MDD."

Major depressive disorder is a leading cause of disability, costing society in excess of $80 billion annually; approximately two-thirds of these costs reflect the enormous disability associated with the disorder. An estimated 15 million people in the United States experience a depressive episode each year, and nearly 17 percent of adults will experience major depression in their lifetime.

"BRITE study results suggest that the ATR biomarker could potentially provide the greatest clinical benefit for those patients who might be receiving a medication that is unlikely to help them," Leuchter said. "Our results suggest that it may be possible to switch these patients to a more effective treatment quickly. This would help patients and their physicians avoid the frustration, risk and expense of long and ineffective medication trials."

Leuchter noted that research has shown that depression patients who do not get better with a first treatment experience prolonged suffering, are more likely to abandon treatment altogether and may become more resistant to treatment over time.

"So the benefits to the individual and to society are enormous," he said.

An added benefit of the biomarker test, according to Leuchter, is that it is non-invasive, painless and fast — about 15 minutes — and only involves the placement of six electrodes around the forehead and on the earlobes.

Aspect Medical Systems, which developed the ATR biomarker, provided financial support for the study. Aspect also participated in the design and conduct of the study; the collection, management, analysis and interpretation of the data; and the preparation and review of the manuscript. Final approval of the form and content of the manuscript rested with the authors.

Other UCLA authors included Dr. Ian Cook, Dr. Karl S. Burgoyne and Dr. James T. McCracken. Leuchter is chair of Aspect's neuroscience advisory board and has provided scientific consultation to them.

The Semel Institute for Neuroscience and Human Behavior is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, institute faculty seek to develop effective treatments for neurological and psychiatric disorders, improve access to mental health services and shape national health policy regarding neuropsychiatric disorders.


Release link :

http://newsroom.ucla.edu/portal/ucla/ucla-researchers-develop-biomarker-101338.aspx

Fall forum at UT Southwestern will focus on genetic causes of Alzheimer's

Dr. Allen Roses, director of Duke University’s Deane Drug Discovery Institute, will discuss research aimed at reducing the risk of Alzheimer’s disease in people most susceptible to it at a Fall Public Forum on Sept. 23 at UT Southwestern Medical Center.

In 1992 Dr. Roses discovered a gene responsible for about half of inherited Alzheimer’s cases, and recently found that another gene interacts with it to further increase a person’s risk. In concert, these genes may account for most of the inherited form of the disease’s genetic effect.

The 7 p.m. forum, presented by The Friends of the Alzheimer’s Disease Center at
UT Southwestern, will be held in the Simmons/Hamon Biomedical Research Buildings on the North Campus. Complimentary valet parking is available, but because seating is limited, attendance should be confirmed by calling the medical center’s Office of Development at 214-648-2344.

“Dr. Roses is truly a great physician-scientist and one of the most important Alzheimer’s disease researchers in the world today,” said Dr. Roger Rosenberg, director of the Alzheimer’s Disease Center. “He discovered 17 years ago the most important genetic risk for developing Alzheimer’s disease and continues to investigate other genes that increase the risk for AD.”

Alzheimer’s disease is predicted to rise to 12 million cases in the U.S. by 2030. Inherited cases of Alzheimer’s represent a fraction of the cases, but they are more severe and start at an earlier age.

Dr. Roses’ recent work defines another gene that plays a major role in the development of Alzheimer’s. His studies may account for 85 percent to 90 percent of the genetic effects.

The Friends of the Alzheimer’s Disease Center was established in 1996 to provide financial support for Alzheimer’s research at UT Southwestern. All of the group’s membership contributions go directly to support Alzheimer’s research at the medical center.

Since its founding, the group has raised more than $600,000 for grants to researchers.


Release link :

http://www.utsouthwestern.edu/utsw/cda/dept353744/files/546701.html

Plastic surgeons should be part of disaster relief planning, response

When a terrorist bomb explodes, a tornado rips through a town, a hurricane devastates a region, or wildfires ravage homes and businesses, plastic surgeons are not typically atop the list of emergency responders.

But they should be, UT Southwestern Medical Center plastic surgeons and disaster experts recommend in the September issue of Plastic and Reconstructive Surgery.

Including plastic surgeons in disaster-relief efforts could improve long-term outcomes for victims of catastrophes, particularly in medical cases that might involve physical scarring and nerve damage, but which can be made worse by lack of quick attention.

“Plastic surgeons are often being overlooked in disaster-planning efforts, particularly in developing medical-team responders,” said Dr. Rod Rohrich, chairman of plastic surgery at
UT Southwestern and the study’s senior author. “Plastic surgeons, particularly those based at academic medical centers and/or major trauma centers, are far more engaged in complex reconstruction procedures on a day-to-day basis than cosmetic surgeons. We are intimately involved in preventing and treating face and tissue scarring, treating burns, and handling sensitive nerve-related injuries, some of which can be best served by having plastic surgeons on the scene or at least near the front lines where disaster victims are being evacuated.”

Examining the on-site evidence of several disasters, the authors identified four pivotal areas in trauma care where plastic surgeons have added expertise:

• soft tissue trauma;
• upper and lower extremity trauma;
• facial trauma; and
• burn management.

The authors suggest that plastic surgeons should be among those who help plan for medical responses prior to disasters, as well part of the responders working in conjunction with traditional surgical responders, such as trauma and orthopaedic surgeons.

The authors examined responses reported in disaster events ranging from devastating earthquakes in Turkey and the London Underground bombings to the Sept. 11 attacks on the East Coast and found a substantial volume of overall cases involving plastic surgery-related issues.

In the case of the London bombings in 2005, facial fractures affected 18 percent of patients. In the Turkey earthquake in 1999, more than 13 percent of hospital beds were occupied by patients needing plastic surgery. In New York City, only 26 percent of burn victims were correctly triaged first to a burn center, despite there being an adequate number of dedicated burn beds in the area.

“Not only should such expert plastic surgeons become part of the disaster preparation team and actual response to applicable incidents, but their training curricula should now also include formal courses in disaster life support and incident command system management,” said Dr. Paul Pepe, chief of emergency medicine at UT Southwestern and an international expert in disaster management. “In essence, both disaster managers and plastic surgery program directors need to foster the contributions of this previously overlooked resource for dealing with catastrophic events.”

Soft tissue injuries, for example, are the most common acute injury from casualties resulting from a blast or explosion and can be treated by other specialties, according to the article. Early intervention by plastic surgeons, however, could help avert problems such as long-term scarring or wound healing and closure, and could be more cost effective.

“Plastic surgeons routinely deal with facial healing, facial fractures, tissue damage and related territory, making access to the expertise of a plastic surgeon invaluable,” Dr. Rohrich said.

Plastic surgeons also bring expertise in tissue viability, amputation and microcirculation issues that can affect whether limbs are preserved, the authors said. Similarly, plastic surgeons have routine experience with burn care that could be invaluable in the case of radiation, biological or fire disasters, as well as help in triaging patients. While other surgical specialists have degrees of expertise in such areas, having direct access to plastic surgeons would be an important asset to disaster medical relief teams.

“As many disciplines gather together to partner in disaster response and preparation, the plastic surgeons should be seen as pivotal members, let alone additional assets, for the medical casualty care team,” the study’s authors concluded.

Visit www.utsouthwestern.org/plasticsurgery to learn more about UT Southwestern’s clinical services in plastic surgery. Visit www.utsouthwestern.org/emergency to learn about clinical services in emergency medicine at UT Southwestern.

Release link :

http://www.utsouthwestern.edu/utsw/cda/dept353744/files/547658.html

Link between depression, early stages of chronic kidney disease found by researchers

One in five patients with chronic kidney disease is depressed, even before beginning long-term dialysis therapy or developing end-stage renal disease, UT Southwestern Medical Center researchers have found.

The study, based on a pool of 272 participants, is the first to examine the rate of depression among these patients using the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM IV), which is considered the gold-standard in evaluating depression.

“Because patients in the early stages of chronic kidney disease are at increased risk for clinical depression, we as nephrologists should consider screening our patients for depression in clinic,” said Dr. Susan Hedayati, assistant professor of internal medicine at UT Southwestern and a staff nephrologist at the Dallas Veterans Affairs Medical Center. She is the lead author of the study, available online and in the current issue of the American Journal of Kidney Diseases.


Previous research has shown that depression rates in the general community are 2 percent to 4 percent; among diabetes patients, 11 percent; among congestive heart failure patients, 14 percent; and among coronary artery disease after heart attack patients, 16 percent.

“Chronic kidney disease patient depression numbers may be higher due to the presence of the same simultaneously occurring conditions that resulted in progressive kidney disease, such as diabetes and atherosclerotic vascular disease,” Dr. Hedayati said. “Alternatively, patients such as diabetics, who are depressed, may develop progressive kidney disease because of non-adherence to medications and physicians’ advice.”

Earlier estimates of depression among chronic kidney disease patients were based on self-report depression scales that can emphasize symptoms such as lack of appetite, weight loss and fatigue. Such symptoms can overlap with other medical conditions, so
UT Southwestern researchers took a novel approach.

From May 2005 to November 2006, researchers invited patients at the Dallas VA Medical Center who were visiting the clinic for chronic kidney disease appointments to join the study. Patients who agreed to participate then underwent a structured clinical interview to determine if they had a current major depressive episode, based on the DSM IV definition of major depressive disorder.

Fifty-seven patients, or 21 percent, were found to be depressed. The mean age of depressed patients was about 65; two were women; and nearly 56 percent were white. All patients were veterans.

The researchers also found that diabetic patients were twice as likely to be depressed as those without diabetes; 63 percent of patients had at least three other medical conditions; and 41 percent had at least four other diseases.

Twenty-six million people in America have chronic kidney disease and millions more are at increased risk, according to the National Kidney Foundation. If treatment does not begin early, the condition progresses to end-stage renal disease. At that point, a patient’s kidneys have failed to the point where dialysis — a filtering of toxic chemicals in the blood and removing fluid to help control blood pressure — or a kidney transplant is needed.

According to the U.S. Renal Data System Annual Report, expenditures for end-stage renal disease patients totaled $15.5 billion, which is approximately 6 percent of the entire Medicare budget, and are projected to consume $28 billion by 2010.

Dr. Hedayati is now conducting the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) to determine whether antidepressant medication would be tolerated in kidney-disease patients and whether such treatment can improve depression.

Other UT Southwestern researchers involved in this study were Dr. Abu Minhajuddin, assistant professor of clinical sciences; Dr. Robert Toto, professor of internal medicine and clinical sciences; and Dr. David Morris, assistant professor of psychiatry. Also involved in the study was Dr. A. John Rush, a former professor of clinical sciences and psychiatry at
UT Southwestern, now vice dean of Duke-NUS Graduate Medical School Singapore.

The study was funded by the Veterans Integrated Service Network 17, Veterans Affairs North Texas Health Care System Research Corporation, the National Institutes of Health and the UT Southwestern O’Brien Kidney Research Core Center.

Visit www.utsouthwestern.org/kidneys to learn more about clinical services at
UT Southwestern for kidney diseases. Visit www.utsouthwestern.org/mentalhealth to learn more about UT Southwestern’s clinical services in psychiatry.


Release link :

http://www.utsouthwestern.edu/utsw/cda/dept353744/files/547326.html

Ice cream may target the brain before your hips, UT Southwestern study suggests

Blame your brain for sabotaging your efforts to get back on track after splurging on an extra scoop of ice cream or that second burger during Friday night's football game.

Findings from a new UT Southwestern Medical Center study suggest that fat from certain foods we eat makes its way to the brain. Once there, the fat molecules cause the brain to send messages to the body's cells, warning them to ignore the appetite-suppressing signals from leptin and insulin, hormones involved in weight regulation.

The researchers also found that one particular type of fat – palmitic acid – is particularly effective at instigating this mechanism.

"Normally, our body is primed to say when we've had enough, but that doesn't always happen when we're eating something good," said Dr. Deborah Clegg, assistant professor of internal medicine at UT Southwestern and senior author of the rodent study appearing in the September issue of The Journal of Clinical Investigation.

"What we've shown in this study is that someone's entire brain chemistry can change in a very short period of time. Our findings suggest that when you eat something high in fat, your brain gets 'hit' with the fatty acids, and you become resistant to insulin and leptin," Dr. Clegg said. "Since you're not being told by the brain to stop eating, you overeat."

Dr. Clegg said that in the animals, the effect lasts about three days, potentially explaining why many people who splurge on Friday or Saturday say they're hungrier than normal on Monday.

Though scientists have known that eating a high-fat diet can cause insulin resistance, little has been known about the mechanism that triggers this resistance or whether specific types of fat are more likely to cause increased insulin resistance. Dr. Clegg said she suspected the brain might play a role because it incorporates some of the fat we eat – whether it is from healthy oils or the not-so-healthy saturated fat found in butter and beef – into its structure.

Based on this suspicion, her team attempted to isolate the effects of fat on the animals' brains. Researchers did this by exposing the animals to fat in different ways: by injecting various types of fat directly into the brain, infusing fat through the carotid artery or feeding the animals through a stomach tube three times a day. The animals received the same amount of calories and fat; only the type of fat differed. The types included palmitic acid, monounsaturated fatty acid and oleic acid.

Palmitic acid is a common saturated fatty acid occurring in foods such as butter, cheese, milk and beef. Oleic acid, on the other hand, is one of the most common unsaturated fatty acids. Olive and grapeseed oils are rich in oleic acid.

"We found that the palmitic acid specifically reduced the ability of leptin and insulin to activate their intracellular signaling cascades," Dr. Clegg said. "The oleic fat did not do this. The action was very specific to palmitic acid, which is very high in foods that are rich in saturated-fat."

Dr. Clegg said that even though the findings are in animals, they reinforce the common dietary recommendation that individuals limit their saturated fat intake. "It causes you to eat more," she said.

The other key finding, she said, is that this mechanism is triggered in the brain – long before there might be signs of obesity anywhere else in the body.

The next step, Dr. Clegg said, is to determine how long it takes to reverse completely the effects of short-term exposure to high-fat food.

Release link :

http://www.utsouthwestern.edu/utsw/cda/dept353744/files/548055.html

World-first swine-flu vaccine trial reveals one dose provides 'strong immune response'

Results from the first swine-flu vaccine trials taking place in Leicester reveal a strong immune response after just one dose.

The pilot study, run by the University of Leicester and Leicester Hospitals, was trialled with 100 healthy volunteers, aged between 18 and 50.

Dr Iain Stephenson, who led the trial at the Leicester Royal Infirmary, said: “The clinical trial of Novartis MF59-adjuvanted cell-based A (H1N1) vaccine indicates that the “swine flu” vaccine elicits a strong immune response and is well-tolerated.

“Results showed that the serum antibody responses were highest among subjects who received two doses of vaccine, however a single vaccine dose also induced responses associated with protection against influenza.

“The findings showed that it is possible to induce protective antibody against A(H1N1) infection within two weeks of administration of a single low-dose adjuvanted vaccine.”

Non-adjuvanted formulations were not evaluated in this part of the study and will be evaluated shortly

The trial evaluated the tolerability and immunogenicity of the vaccine, and tested different schedules of vaccination, in terms of time between vaccinations. The vaccine schedule was one or two doses of 7.5μg MF-59 adjuvanted surface-antigen A/California/2009 vaccine derived from cell-culture.

Dr. Stephenson, of the Department of Infection, Immunity and Inflammation at the University of Leicester is a clinical senior lecturer at the University, and a consultant in infectious diseases at the University Hospitals of Leicester NHS Trust. He said: “The aim of the trial was to find out how many doses and what type of vaccine is needed to give protection. These initial results should help to plan vaccination campaigns in the autumn, including doses and timings. We concluded that the MF59-adjuvanted A(H1N1) vaccine of low antigen content was well tolerated and generated antibody responses associated with protection against influenza, even after a single dose.”

“The results suggest that one vaccine dose may be sufficient to protect against the A(H1N1) swine flu, rather than two. Larger trials are already underway around the world. Timings on when the vaccine will be available to governments will depend on the results of these clinical trials, and approvals by regulatory authorities’’

The research found the vaccine is well tolerated with pain at the injection site the most frequent adverse event.

Additional pivotal trials with both cell culture and traditional egg based vaccines under way around the world that will include more than 6000 adults and children.

Previous research had indicated that two doses of the vaccine would be needed against swine flu. You can access earlier stories here:

http://www2.le.ac.uk/ebulletin/news/press-releases/2000-2009/2009/08/nparticle.2009-08-11.3248230936

You can view the press release from Novartis here:

http://www.novartis.com/newsroom/media-releases/en/2009/1339223.shtml


Release link :

http://www2.le.ac.uk/ebulletin/news/press-releases/2000-2009/2009/09/nparticle.2009-09-03.6831410081

Low vitamin D raises heart disease risks in diabetics

Low levels of vitamin D are known to nearly double the risk of cardiovascular disease in patients with diabetes, and researchers at Washington University School of Medicine in St. Louis now think they know why.

They have found that diabetics deficient in vitamin D can't process cholesterol normally, so it builds up in their blood vessels, increasing the risk of heart attack and stroke. The new research has identified a mechanism linking low vitamin D levels to heart disease risk and may lead to ways to fix the problem, simply by increasing levels of vitamin D.

"Vitamin D inhibits the uptake of cholesterol by cells called macrophages," says principal investigator Carlos Bernal-Mizrachi, M.D., a Washington University endocrinologist at Barnes-Jewish Hospital. "When people are deficient in vitamin D, the macrophage cells eat more cholesterol, and they can't get rid of it. The macrophages get clogged with cholesterol and become what scientists call foam cells, which are one of the earliest markers of atherosclerosis."

Macrophages are dispatched by the immune system in response to inflammation and often are activated by diseases such as diabetes. Bernal-Mizrachi and his colleagues believe that in diabetic patients with inadequate vitamin D, macrophages become loaded with cholesterol and eventually stiffen blood vessels and block blood flow.

Bernal-Mizrachi, an assistant professor of medicine and of cell biology and physiology, studied macrophage cells taken from people with and without diabetes and with and without vitamin D deficiency. His team, led by research assistants Jisu Oh and Sherry Weng, M.D., exposed the cells to cholesterol and to high or low vitamin D levels. When vitamin D levels were low in the culture dish, macrophages from diabetic patients were much more likely to become foam cells.

In the Aug. 25 issue of the journal Circulation, which currently is available online, the team reports that vitamin D regulates signaling pathways linked both to uptake and to clearance of cholesterol in macrophages.

"Cholesterol is transported through the blood attached to lipoproteins such as LDL, the 'bad' cholesterol," Bernal-Mizrachi explains. "As it is stimulated by oxygen radicals in the vessel wall, LDL becomes oxidated, and macrophages eat it uncontrollably. LDL cholesterol then clogs the macrophages, and that's how atherosclerosis begins."

That process becomes accelerated when a person is deficient in vitamin D. And people with type 2 diabetes are very likely to have this deficiency. Worldwide, approximately one billion people have insufficient vitamin D levels, and in women with type 2 diabetes, the likelihood of low vitamin D is about a third higher than in women of the same age who don't have diabetes.

The skin manufactures vitamin D in response to ultraviolet light exposure. But in much of the United States, people don't make enough vitamin D during the winter — when the sun's rays are weaker and more time is spent indoors.

The good news is when human macrophages are placed in an environment with plenty of vitamin D, their uptake of cholesterol is suppressed, and they don't become foam cells. Bernal-Mizrachi believes it may be possible to slow or reverse the development of atherosclerosis in patients with diabetes by helping them regain adequate vitamin D levels.

"There is debate about whether any amount of sun exposure is safe, so oral vitamin D supplements may work best," he says, "but perhaps if people were exposed to sunlight only for a few minutes at a time, that may be an option, too."

He has launched a new study of diabetics who are both deficient in vitamin D and have high blood pressure. He wants to learn whether replacing vitamin D will lower blood pressure and improve blood flow. For this study, Bernal-Mizrachi is recruiting patients with type 2 diabetes ages 30 to 80 who are not taking insulin to control their blood sugar. Study volunteers also must have high blood pressure.

release link :

http://mednews.wustl.edu/news/page/normal/14489.html

Chronic lymphatic leukemia

Chronic lymphatic leukemia (CLL) is the most common form of blood cancer in adults. About 120,000 people in Europe and the USA are affected – most of them over the age of 50.


It is still not known what causes the disease. Among the possibilities discussed are certain kinds of radiation, chemicals, viruses, and genetic factors. One characteristic of CLL is the accumulation of functionally immature white blood corpuscles (lymphocytes) in the bone marrow, the blood, lymphatic tissue and other organs. Lymphocytes occur in the blood in two different forms: as B-cells and T-cells. In 95 percent of all cases of CLL, it is the B-lymphocytes that are affected.

The mutated B-cells live longer than normal, healthy blood cells. The accumulation of functionally immature cells in the marrow impedes the formation of healthy cells and can cause death. Today, all patients must live with the knowledge that CLL is currently incurable. However, in the meantime there are innovative forms of treatment which make it possible to markedly prolong life and improve the patients' quality of life.


Symptom-free for a long time:

A distinction is generally made between the acute and chronic forms of leukemia. Unlike the acute forms, the chronic forms, of which CLL is one, often cause no complaints at all for a long time. Occasionally, CLL is detected by pure coincidence during a routine blood test. Sometimes, however, it can also be indicated by diffuse symptoms such as tiredness, fever, sudden weight loss, night-time sweating, unusually frequent colds or infections, swollen glands in the nape of the neck, the inside of the elbow or groin, or a swollen spleen.It is therefore often not diagnosed – or treated – until quite late in the course of the disease.

Still no cure, but a longer life:

Just a few decades ago there was practically no treatment at all for chronic lymphatic leukemia (CLL). In the meantime, however, several drugs have become available. Although they do not lead to a complete cure, they do at least improve the patients' quality of life. As a rule, CLL is first combated with chemotherapy. So-called alkylating substances play an important role here. Sometimes a combination of several such substances is used. If the patient responds to the therapy, the blood-cell count returns to normal – and the quality of life improves. As so often in tumor therapy, however, the insidious thing is that individual malignant cells can survive this initial therapy. After multiplying further, they can even become resistant to the chemotherapeutic agent(s). Then another therapy becomes necessary, the so-called second-line therapy. A substance has been available since 1991 that selectively changes the genetic constitution of the malignant cells. This blocks enzymes that are necessary for cell division. The result is that the malignant cells cannot multiply. An important success in the fight against CLL.


New hope: antibodies:

In the meantime, antibodies have also proved their worth alongside classic chemotherapeutic agents in the fight against CLL. These are structured in such a way that they perfectly fit onto a protein on the surface of lymphocytes. In this way, the antibody marks these cells in a way that is visible to the body's own immune system. The command that goes with it is: "Destroy the cell." After treatment, the remaining stem cells can subsequently supply healthy lymphocytes, so that the immune system is regenerated. In studies, the antibody has also proved effective as a first-line therapy.


Release link :

http://www.bayerscheringpharma.de/scripts/pages/en/health/oncology/chronic_lymphatic_leukemia/index.php

Breast MRI doubles DCIS detection rate compared with mammography

Magnetic resonance imaging (MRI) of the breast doubles the rate at which ductal carcinoma in situ (DCIS) is detected, and even picks up cases of this early stage tumor that conventional mammography misses.

Reporting their findings in The Lancet, Christiane Kuhl and colleagues from the University of Bonn in Germany comment: "Our study suggests that the sensitivity of film screen or digital mammography for diagnosing DCIS is limited."Of 167 intraductal cancers that had been diagnosed during the study period, 72 (43%) were mammographically occult, but were diagnosed by MRI alone," say Kuhl and team.


They conducted a prospective, observational study that initially involved over 7300 women referred to their institution between 2002 and 2006 for diagnostic assessment and breast screening.Of these women, 193 were given a final surgical pathological diagnosis of DCIS, and 167 of these had both screening mammograms and MRI scans taken before biopsy and were the focus of the team's investigation.Comparing the sensitivities of mammography and MRI to detect all cases of DCIS, Khul and team found that mammography detected 93 (56%) cases and MRI detected 153 (92%) cases (p<0.0001)."of>

Kuhl and team note that while these results support the widespread use of MRI to detect DCIS, their results may not be reproducible in community breast screening services at present."Since breast MRI is currently used only rarely in clinical practice, for the time being, few radiologists can offer a level of expertise for MRI that comes close to that required for diagnostic mammography."They call for a "multi-institutional screening trial" to further investigate the role of MRI for diagnosing DCIS. A comment echoed in an accompanying editorial."These findings can only lead to the conclusion that MRI outperforms mammography in tumor detection and diagnosis," Carla Boetes and Ritse Mann from Radboud University Nijmegen Medical Center in The Netherlands also write in The Lancet."MRI should no longer be regarded as an adjunct to mammography but as a distinct method to detect breast cancer in its earliest stage. A large multicenter breast-screening trial with MRI in the general population is essential."

Release link :

http://www.breastcancersource.com/breastcancersourceHCP/6096_28015___.aspx

News From The Journal Of Neuroscience

1. Docking and Priming with Munc18

Attila Guly's-Kov'cs, Heidi de Wit, Ira Milosevic, Olexiy Kochubey, Ruud Toonen, J'rgen Klingauf, Matthijs Verhage, and Jakob B. S'rensen

This week, Guly's-Kov'cs et al. unmask a dual role for Munc18 in docking and priming of vesicles in chromaffin cells. In vitro, Munc18 binds the "closed" state of syntaxin1 and thus occludes binding of the SNARE proteins SNAP-25 and synaptobrevin. However, Munc18 cannot be simply a negative regulator of exocytosis because vesicles fail to dock in its absence. To address this issue, the authors expressed mutant variants in chromaffin cells from Munc18 null mice and used uncaging of calcium to trigger release of primed vesicles. Expression of the NV mutation that prevents binding to closed syntaxin1 reduced vesicle docking. However, Munc18-1 NV rescued release, albeit to a lesser extent than wild type. Thus, Munc18 regulates a postdocking (priming) step by a mechanism that does not require binding to syntaxin1. In fact, the authors suggest that this second interaction either involves dissociation from syntaxin or a conformational change in the N-terminal domain of Munc18.



2. Pak1 and Neuronal Polarity

Tom Jacobs, Frederic Causeret, Yoshiaki V. Nishimura, Mami Terao, Adele Norman, Mikio Hoshino, and Margareta Nikolic

If you want to make axons, you will need some activated p21-activated kinase (Pak1), according to Jacobs et al. The authors found this CdC42 and cofilin effector in all neurites, but it was activated locally in nascent axons. In cultured hippocampal and cortical neurons, the levels of membrane-associated phosphorylated active) Pak1 peaked at the same time that neurons became polarized with distinct axons and dendrites, at ~ 2--4 d in Vitro (DIV). Total Pak1, in contrast, reached a plateau at 4 DIV and beyond. Total and activated Pak1 were evenly distributed among multiple neurites before polarization, but once a neurite emerged as the axon, activated Pak1 was restricted to the soma and the distal part of the nascent axon, where it reorganized the F-actin cytoskeleton. Expression of constitutively active Pak1 disrupted morphological development of dendrites and axons; neurons did not survive past 7 DIV when Pak1 expression was silenced by RNA interference.


3. Toward an Auditory Midbrain Implant

Hubert H. Lim and David J. Anderson

Cochlear implants have revolutionized the treatment of sensorineural hearing loss, but they don't work for everyone, for example, if the auditory nerve is severely damaged. Lim and Anderson propose the inferior colliculus central nucleus (ICC) as an alternative site for auditory prostheses. For such devices to work, it is necessary to stimulate at sites that tap into the tonotopic organization of the auditory system; but there's more. In this week's Journal, the authors reveal a previously unappreciated complexity in the functional organization of ICC. In anesthetized guinea pigs, the authors stimulated along the isofrequency or rostrocaudal axis in ICC. They measured responses in primary auditory cortex including threshold, evoked potential magnitude, discriminable level steps, and temporal response patterns. These parameters generally were optimal at rostral and slightly ventral ICC stimulation sites. At least two functional regions emerged, one caudal--dorsal and one rostral--ventral, which will require consideration in designing implants.

4. Microglia, Complement, and Neuropathic Pain

Robert S. Griffin, Michael Costigan, Gary J. Brenner, Chi Him Eddie Ma, Joachim Scholz, Andrew Moss, Andrew J. Allchorne, Gregory L. Stahl, and Clifford J. Woolf

In this week's Journal, Griffin et al. used microarrays to narrow in on genes affected in three peripheral nerve injury models of neuropathic pain. The most highly regulated were involved in the microglial complement cascade. Messenger RNAs for C1qb, C3, and C4 were upregulated in the dorsal horn of the spinal cord after injury and were expressed only in microglia. The complement cascade culminates in C5 and C5a receptor (C5aR) activation and formation of the membrane attack complex (MAC). Both C5 and C5aR were upregulated dramatically after injury. Mice lacking C5 displayed reduced postinjury indicators of neuropathic pain, whereas animals lacking the MAC component C6 did not. Having ruled out C3a and the MAC as major pain effectors, the authors injected naive rats intrathecally with the C5a anaphylatoxin. C5a increased cold pain sensitivity, and a C5a receptor antagonist blocked this effect, consistent with a role for C5a in neuropathic pain.

Rlease link :

http://www.medicalnewstoday.com/articles/79114.php