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New research from the University of Virginia Health System shows that, when combined, two emerging medical technologies hold significant promise for treating the most deadly and... devastating form of brain tumor, glioblastoma multiforme (GBM).

According to Jason Sheehan, M.D., a neurosurgeon and assistant professor of neurosurgery at the UVA School of Medicine, the use of controlled-released nanoparticles containing chemotherapeutic drugs and non-invasive ultrasound successfully helps to treat GBM tumors in mice.

Sheehan discussed the findings on May 4 during the annual meeting of the American Association of Neurological Surgeons (AANS). The association selected Sheehan for its 2009 Young Investigator Award in recognition of his outstanding potential as a researcher in the field of neuro-oncology.

During the study, Sheehan and his colleagues placed a cancer-killing drug inside nanoparticles affixed to microbubbles (which are the size of red blood cells) and injected the compound into the veins of immunocompromised mice. Carried by the bloodstream, the treatment travelled to the GBM tumor site. There, a 1 MHz dose of energy from the ultrasound equipment caused the microbubbles to burst and release the drug directly onto the cancer cells. Results show the treatment reduced tumor cell viability in a significant fashion and compared favorably with an anti-cancer drug, administered to the study's positive control group. The UVA study also showed ultrasound induced damage to the microvessels feeding the tumor.

"Many drugs that kill GBM cells in vitro prove ineffective in living organisms because they are not able to penetrate the blood brain barrier," noted Sheehan. "These new technologies are allowing us to overcome this challenging problem and deliver a highly targeted and sustained release of chemotherapy drugs. Although more research is needed, our findings indicate the technologies hold significant promise for patients with high grade gliomas and other malignant brain tumors."

Sheehan's research is on-going and is being performed in collaboration with his study co-authors, Caitlin Burke, BS, a graduate student in the UVA School of Engineering and Applied Science and Richard Price, PhD., a biomedical engineer in the UVA School of Medicine. Their research is funded by multi-year grants from the Hartwell Foundation.

"I'm honored to receive the 2009 AANS Young Investigator Award," Sheehan says.

Sponsored by the American Brain Tumor Association, the award is presented annually by the American Association of Neurological Surgeons to a young faculty member in neurosurgery.

Sheehan received his B.S., M.S., PhD, and M.D. from the University of Virginia. His B.S. is in Chemical Engineering with the highest honors awarded from the School of Engineering. He performed fellowships at Auckland University and the University of Pittsburgh. Sheehan won the University of Virginia Clinical Excellence Award in 2006.

Widely-published, Sheehan is author of more than 100 peer-reviewed papers as well as numerous invited manuscripts and a book. He reviews manuscripts for several medical journals and serves on a variety of professional committees. Sheehan's memberships include the American Association of Neurological Surgeons (AANS), the American College of Surgeons, Leksell Gamma Knife Society, Neurosurgical Society of the Virginias, AANS/CNS Tumor Section, and the American Society of Stereotactic and Functional Neurosurgeons.

Sheehan's laboratory team also pursues translational and basic science research in brain tumors.

Source: University of Virginia Health System

A phase III study has shown that adding an antibody-based therapy that harnesses the body's immune system resulted in a 20 percent increase in the number of children living disease-free for... at least two years with neuroblastoma. Neuroblastoma, a hard-to-treat cancer arising from nervous system cells, is responsible for 15 percent of cancer-related deaths in children. The researchers reported their findings - the first to show that immunotherapy could be effective against childhood cancer - online May 14, 2009 on the American Society of Clinical Oncology website in advance of presentation June 2.

"This establishes a new standard of care for a traditionally very difficult cancer in children," said lead author Alice Yu, MD, PhD, professor of pediatric hematology/oncology at the University of California, San Diego School of Medicine and the Moores UCSD Cancer Center. "High-risk neuroblastoma has always been a frustrating cancer to treat because, despite aggressive therapy, it has a high relapse rate."

The therapy targets a specific glycan (a complex sugar chain found on the surface of cells) on neuroblastoma cells called GD2, which inhibit the immune system from killing cancer cells. The antibody - ch14.18 - binds to this glycan, enabling various types of immune cells to attack the cancer.

Neuroblastoma - in which the cancer cells arise from nerve cells in the neck, chest, or abdomen - is the most common cancer diagnosed in the first year of life. Approximately 650 new cases of neuroblastoma are diagnosed in this country every year, and about 40 percent of patients have high-risk neuroblastoma. These high-risk patients are usually treated with surgery, intensive chemotherapy with stem cell rescue (in which patients' adult stem cells, removed before treatment, are returned after chemotherapy to restore the blood and immune system), and radiation therapy. Still, only 30 percent of patients survive.

Yu and her colleagues compared both the percentage of patients who were still alive without experiencing a recurrence after two years as well as overall survival in two groups of 113 patients each. Patients began the trial when they were newly diagnosed with high-risk neuroblastoma. After conventional treatment with surgery, chemotherapy, stem cell rescue and radiotherapy, one group was given the standard treatment (retinoic acid) plus immunotherapy (the antibody plus immune-boosting substances), while 113 similar patients received the standard treatment alone.

After two years, 66 percent of individuals in the immunotherapy group were living free of cancer compared to 46 percent in the standard treatment group. Overall survival improved significantly as well. The trial patient randomization was halted early because of the benefit seen, and all patients enrolled in the trial will receive immunotherapy plus standard treatment.

Yu noted that the two-year mark is especially important because past trials have shown that those neuroblastoma patients who live without disease for two years after a stem cell transplant will most likely be cured.

"This is the first time in many years that we have been able to improve the 'cure rate' for neuroblastoma patients," she said. "This new therapy can help us improve care and perhaps offer new hope to many patients and families."

Yu and her team conducted the early phase I and phase II trials at the General Clinical Research Center at UC San Diego Medical Center.

Other co-authors include Andrew Gilman, Carolinas Medical Centre; M. Fevzi Ozkaynak, New York Medical College; Susan Cohn, University of Chicago; John Maris, Children's Hospital of Philadelphia; Paul Sondel, University of Wisconsin; W. B. London, University of Florida; S. Kreissman, Duke University; H.X. Chen, National Cancer Institute; and K.K. Matthay, UCSD. Local patients were seen in San Diego at Rady Children's Hospital.

Source:
Steve Benowitz
University of California - San Diego

It takes less than a minute for a stroke to change a person's life forever, but taking the time to make a few simple lifestyle adjustments and finding out how to recognize an attack when... it happens can save thousands of lives.

"It is the third leading cause of death in the United States and the leading cause of adult disabilities, but more than half of all strokes can be prevented," says Dr. Matthew Fink, chief of the Division of Stroke and Critical Care Neurology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

These few lifestyle changes can greatly reduce anyone's chances of having a stroke:

- Reduce salt intake. High blood pressure is one of the leading causes of stroke. Cutting back on salt is one of the most significant steps to maintaining or lowering your blood pressure to a healthy level of 120/80 or below. Try flavoring your food with a variety of spices that may be healthier than salt.

- Eat a heart-healthy diet. Maintaining a healthy balance between your good cholesterol (HDL) and bad cholesterol (LDL) is the best way to prevent high cholesterol, heart disease and the increased risk of stroke. Your cholesterol level should remain at 200 mg/dl or below.

- Stop smoking. Smoking is not only bad for your lungs, it is bad for your brain, too. A smoker is at twice the risk of having a stroke because smoking damages blood vessels, raises blood pressure and speeds up the clogging of arteries.

- Exercise. If you are obese or overweight, your risk factors for high cholesterol, high blood pressure and diabetes increases and so does your risk for a stroke. Extra weight places an added strain on your entire circulatory system, but aerobic exercise can be a good way to lose those extra pounds and substantially improve your health.

However, there are certain populations that are still at higher risk of having a stroke even after making the proper lifestyle changes. These include adults 55 years of age or older, African-Americans and Hispanics, those with a family history of stroke, and people who have already had an attack or a transient ischemic attack (mini stroke). In addition, women are more likely to die from a stroke than men, although attacks are more common in men.

"When someone does have a stroke they may experience either slight or extremely noticeable physical changes. The most effective way to prevent the permanent damage associated with stroke is to recognize the signs of an attack and to seek medical attention immediately," says Dr. Randolph Marshall, director of the Stroke Division at NewYork-Presbyterian Hospital/Columbia University Medical Center.

The most common signs of a stroke are:

- Numbness. A sudden numbness or weakness in the face, arms or legs -- specifically on one side of the body.

- Trouble Speaking. A feeling of confusion and slurred speech or trouble speaking.

- Loss of Balance. Dizziness and trouble walking.

- Poor Eyesight. A loss of vision in one or both of the eyes.

- Headache. A sudden headache that occurs for no apparent reason.

"Eighty percent of all strokes are caused by a blood clot that blocks blood flow to the brain. Today there are many new drugs and techniques that when applied during the early onset of an attack can prevent, and in some cases reverse, the damage caused by these blockages," says Dr. Philip Stieg, chairman of the Department of Neurological Surgery and neurosurgeon-in-chief at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Some of the most popular techniques include:

- Revascularization. Tiny micro catheters such as the Merci Retriever and the Penumbra System are inserted into the artery and used to remove the blockages and reopen the artery.

- Clot-Dissolving Drugs. Tissue Plasminogen Activator (t-PA) is a commonly used clot-dissolving drug that is injected into the artery and dissolves the clot, restoring blood flow to the brain. This procedure is most effective when used immediately following an attack.

Source
NewYork-Presbyterian Hospital

Researchers at Intermountain Medical Center in Salt Lake City believe that they have made a breakthrough connection between atrial fibrillation, a fairly common heart rhythm disorder, and... Alzheimer's disease, the leading form of dementia among Americans.

In a study presented May 15, at "Heart Rhythm 2009," the annual scientific sessions of the Heart Rhythm Society in Boston, researchers unveiled findings from the study of more than 37,000 patients that showed a strong relationship between atrial fibrillation and the development of Alzheimer's disease.

The study, which drew upon information from the Intermountain Heart Collaborative Study, a vast database from hundreds of thousands of patients treated at Intermountain Healthcare hospitals, found:

* Patients with atrial fibrillation were 44 percent more likely to develop dementia than patients without the heart disorder.

* Younger patients with atrial fibrillation were at higher risk of developing all types of dementia, particularly Alzheimer's. Atrial fibrillation patients under age 70 were 130 percent more likely to develop Alzheimer's.

* Patients who have both atrial fibrillation and dementia were 61 percent more likely to die during the study period than dementia patients without the rhythm problem.

* Younger atrial fibrillation patients with dementia may be at higher risk of death than older AF patients with dementia.

Intermountain Medical Center cardiologist T. Jared Bunch, M.D., the study's lead researcher, presented the findings at the scientific session.

"Previous studies have shown that patients with atrial fibrillation are at higher risk for some types of dementia, including vascular dementia. But to our knowledge, this is the first large-population study to clearly show that having atrial fibrillation puts patients at greater risk for developing Alzheimer's disease," said Dr. Bunch.

Alzheimer's is a devastating brain disease affecting approximately 5.3 million Americans. It is the most common form of dementia (a general term for life-altering loss of memory and other cognitive abilities), and accounts for 60-80 percent of all dementia cases. Today, it is the sixth leading cause of death in the United States.

Currently, the known risk factors for Alzheimer's are age, family history and genetics, though injury may also be linked with the disease. Heart health has long been suspected to play a role, but has not been linked. The Intermountain Medical Center study bolsters that connection.

"The study shows a connection between atrial fibrillation and all types of dementia," said Bunch. "The Alzheimer's findings - particularly the risk of death for younger patients - break new ground."

Atrial fibrillation is the most common heart rhythm problem, affecting about 2.2 million Americans. It occurs when the heart beats chaotically, leading blood to pool and possibly clot. If the clot leaves the heart, a stroke can result.

The Intermountain Medical Center study looked at five years of data for 37,025 patients. Of that group, 10,161 developed AF and 1,535 developed dementia during the study period.

The study authors say more research is needed to explore further the relationship between atrial fibrillation and the development of Alzheimer's disease.

"Now that we've established this link, our focus will be to see if early treatment of atrial fibrillation can prevent dementia or the development of Alzheimer's disease," says cardiologist John Day, M.D., director of heart rhythm services at Intermountain Medical Center and a co-author of the study.

Source:
Jess Gomez
Intermountain Medical Center

For many years, it has been known that aspirin is beneficial to patients suffering heart attacks and near-heart attacks. But which of the many different types of.. aspirin is likely to help the most?

A group of researchers led by Dr. Sean Nordt from the University of California, San Diego gave three different types of aspirin to a group of volunteer research subjects: regular aspirin swallowed whole, regular aspirin chewed and swallowed, and chewable aspirin chewed and swallowed. Blood levels of aspirin were then measured, to see which route led to the highest aspirin levels in the body.

The chewable aspirin consistently showed greater and more rapid absorption than the regular aspirin, whether swallowed whole or chewed. This seemingly quite simple finding could lead to improvements in the care of heart attack patients.

The presentation, entitled "Comparison Of Three Aspirin Formulations" was given by Dr. Sean Nordt in the Cardiovascular forum at the 2009 SAEM Annual Meeting at the Sheraton New Orleans on May 15. Abstracts are published in Vol. 16, No. 4, Supplement 1, April 2009 of Academic Emergency Medicine, the official journal of the Society for Academic Emergency Medicine.

Source:
Sean Wagner
Wiley-Blackwell

Treating a common heart rhythm disorder by burning heart tissue with a catheter works dramatically better than drug treatments, a major international study has found.

One year after undergoing a treatment called catheter ablation, 63 percent of patients with an irregular heartbeat called atrial fibrillation were free of any recurrent atrial arrhythmias or symptoms. By comparison, only 17 percent of those treated with drugs were arrhythmia-free. Results were so convincing the trial was halted early.

The ablation group also scored significantly higher on a quality-of-life scale.

The study included 167 patients at 19 centers, including 15 centers in the United States. Lead researcher Dr. David Wilber presented results at Heart Rhythm 2009, the Society's 30th Annual Scientific Sessions. Wilber is director of the Cardiovascular Institute at Loyola University Stritch School of Medicine in Maywood, Il.

Atrial fibrillation, often called A-Fib, is the most common form of irregular heartbeat. Electrical signals, which regulate the heartbeat, become erratic. Instead of beating regularly, the upper chambers of the heart quiver. Not all the blood gets pumped out, so clots can form. Atrial fibrillation can lead to strokes and heart failure.

A-Fib patient Robin Drabant, 35, of Hanover Park, Il., said the condition once "made me feel like I was 90 years old with a failing heart." She was on a maximum dose of an A-Fib medication, which caused fatigue. Despite the drug, she still had episodes almost every day, lasting from 10 seconds to an hour or longer. "I would lose my breath and could feel my heart racing and fluttering," she said.

Wilber performed a catheter ablation on Drabant in May, 2008, and she no longer has A-Fib episodes. "I had great results," she said.

A-Fib symptoms include heart palpitations, dizziness, fatigue, shortness of breath and fainting. "A lot of people are disabled," Wilber said. "They have no energy. They can't work. They have a very poor quality of life."

More than 2 million Americans have atrial fibrillation, and there are about 160,000 new cases each year. The number is increasing, due in part to the aging population and the obesity epidemic.

Drugs such as beta blockers and calcium channel blockers can slow the heart rate during an A-Fib episode. Other drugs such as flecainide and propafenone can help maintain a normal rhythm. When drugs don't work or produce unacceptable side effects, alternative treatments include a pacemaker, surgery and catheter ablation.

In the ablation procedure, an electrophysiologist destroys small areas of heart tissue that are responsible for the erratic electrical signals. A catheter (thin flexible tube) is guided through blood vessels to the heart. The tip of the catheter delivers radiofrequency energy that heats and destroys tissue. Possible adverse effects include irritation of the lining of the heart, fluid in the lungs or around the heart, bleeding, clots and stroke.

In the study, 106 patients with frequent episodes of atrial fibrillation were randomly assigned to undergo ablation and 61 similar patients were randomly assigned to receive drug therapy. All patients had experienced at least three episodes of atrial fibrillation during the previous six months and had failed at least one attempt to control the rhythm with drugs.

The study was funded by Biosense Webster, which makes the ThermoCool catheter used in the trial. Wilber is a consultant to the company.

The study was the largest to date to compare ablation to drug therapy for atrial fibrillation. Earlier studies involved single centers and smaller sample sizes, Wilber said. An additional study called CABANA is designed to determine whether ablation patients live longer than patients receiving medication. Researchers will follow about 3,000 patients for three years.

Heart Rhythm 2009 May 13-16 at the Boston Exhibition and Convention Center.

Source:
Jim Ritter
Loyola University Health System

PLC Systems Inc. (OTC Bulletin Board: PLCSF), a company focused on innovative cardiac and vascular medical device-based technologies, announced that it will demonstrate its RenalGuard System(TM) at EuroPCR, the annual meeting of... the European Association of Percutaneous Cardiovascular Interventions (EAPCI), May 19-22, 2009, in Barcelona, Spain. More than 11,000 clinicians and professionals are expected to attend this event.

In addition, RenalGuard(R) will be included as part of a live case transmission from Hospital Clinico San Carlos, Madrid, Spain during the meeting. The interventional cardiologists involved in the case plan to demonstrate how RenalGuard is used to help prevent Contrast-Induced Nephropathy (CIN) in a patient with impaired renal function undergoing a Percutaneous Coronary Intervention (PCI).

"Following the spirit of EuroPCR, our commitment during these live cases is to provide valuable clinical education to EuroPCR attendees," stated Dr. Javier Escaned, Consultant Interventional Cardiologist, Hospital Clinico. "I consider that creating awareness of the problem of CIN and disseminating new information on how to prevent it are very important."

Mark R. Tauscher, president and chief executive officer of PLC Systems, said, "We are very pleased to be presenting RenalGuard to this important audience, and especially pleased that Dr. Escaned will be demonstrating a live case illustrating how RenalGuard works and how it may benefit patients. CIN is a significant and growing concern worldwide, and we are very encouraged by the prospect that RenalGuard could remedy it."

Currently, RenalGuard is the subject of an investigator-sponsored trial to study its efficacy in mitigating against CIN at the University of Milan-Centro Cardiologico Monzino (CCM). The trial is designed to provide an assessment of the potential benefits of induced diuresis with matched hydration therapy compared to standard overnight hydration, a prevalent method of treatment in the EU, in the prevention of CIN in patients undergoing cardiac catheterization procedures and percutaneous coronary interventions with baseline impairment in renal function. The CIN-prevention therapy of induced diuresis and matched hydration therapy will be provided using RenalGuard.

PLC received the CE Mark Certificate for the RenalGuard System in December 2007, and concluded its pilot safety trial in the U.S. late in 2007. The company has received full approval from the FDA to commence a U.S. pivotal trial to study the effectiveness of RenalGuard in the prevention of CIN. In March 2008, PLC signed its first international distribution agreement for RenalGuard with Artech s.r.l., Cavezzo, Italy for distribution of its RenalGuard System into Italy, and in May 2009, PLC announced its second European distributor, IZASA Distribuciones Tecnicas S.A., headquartered in Barcelona, Spain, for the distribution of RenalGuard in Spain.

About PLC Systems Inc.

PLC Systems Inc. is a medical technology company specializing in innovative technologies for the cardiac and vascular markets. Headquartered in Franklin, Massachusetts, PLC pioneered the CO2 Heart Laser System, which cardiac surgeons use to perform CO2 transmyocardial revascularization (TMR) to alleviate symptoms of severe angina. PLC's newest product, RenalGuard, is approved for sale in the EU as a general fluid balancing device.

This press release contains "forward-looking" statements. For this purpose, any statements contained in this press release that relate to prospective events or developments are deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will" and similar expressions are intended to identify forward-looking statements. Our statements of our objectives are also forward-looking statements. While we may elect to update forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our estimates change, and you should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. Actual results could differ materially from those indicated by such forward-looking statements as a result of a variety of important factors, including that we may not receive necessary regulatory approvals to market our RenalGuard product or that such approvals may be withdrawn, we may be unable to raise sufficient funds in the future to implement our business plan and/or commence our planned U.S. clinical trial for RenalGuard, the current clinical trial in Italy and the planned future U.S. clinical trial for RenalGuard as a safe and effective prevention device for contrast induced nephropathy may not be completed in a timely fashion, if at all, or, if these clinical trials are completed, they may not produce clinically significant or meaningful results, the RenalGuard product may not be commercially accepted, operational changes, competitive developments may affect the market for our products, regulatory approval requirements may affect the market for our products, and additional risk factors described in the "Forward Looking Statements" section of our Annual Report on Form 10-K for the year ended December 31, 2008, and our other SEC reports.

PLC Systems, PLC Medical Systems, PLC and CO2 Heart Laser, RenalGuard and RenalGuard System are trademarks of PLC Systems Inc.

Source: PLC Systems Inc

The US Food and Drug Administration has written a warning letter to General Mills, the makers of the popular breakfast cereal Cheerios, explaining that they have reviewed the labelling of the product and found it contains "serious violations" of federal regulations.

The details of the FDA findings are in a letter dated May 5th, from W Charles Becoat, FDA Director for the Minneapolis District, to... Ken Powell, Chairman and CEO of Minneapolis-based General Mills, who make Cheerios.

According to the FDA, General Mills is breaking federal regulations on two counts: they are marketing Cheerios like an "unapproved new drug" and misbranding the product by making "unauthorized health claims".

The FDA letter to the food company states:

"FDA's review found serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) and the applicable regulations in Title 21, Code of Federal Regulations (21 CFR)."

The FDA said that the Cheerios product label promotes it like a drug intended for use in the "prevention, mitigation, and treatment of disease". The letter drew particular attention to phrases that say the product lowers cholesterol by "4 per cent in 6 weeks", that it can also reduce bad cholesterol by 4 per cent, and that it is "clinical proven" to lower cholesterol.

The letter does not address the veracity of the claims, it addresses the point that by making such claims then the product is really a drug and should go through the proper channels for obtaining drug approval.

For example, as the letter explains, the claims indicate that Cheerios is:

"Intended for use in lowering cholesterol, and therefore in preventing, mitigating, and treating the disease hypercholesterolemia."

And by claiming that the product lowers total and bad cholesterol, then it is also claiming to treat heart disease, for which total and bad (LDL) cholesterol are known risk factors. This is what puts the product in the "new drug" category, and the letter quotes several sections of "the Act" to support their case.

The FDA said another reason that the product is considered to be a "new drug" was because under another section of "the Act", it is "not generally recognized as safe and effective for use in preventing or treating hypercholesterolemia or coronary heart disease".

The letter acknowledged that General Mills had observed regulations correctly in respect of a health claim associating "soluble fiber from whole grain oats with a reduced risk of coronary heart disease", but the two claims about lowering cholesterol are not part of that, and goes into great detail about the positioning on the packet label and how the words are shown to make its case.

The FDA said that even if the cholesterol-lowering claim could be argued to be part of an otherwise permissible claim, the wording disqualifies it from use in the soluble fiber health claim.

On the issue of misbranding, the FDA said that Cheerios bears "unauthorized health claims in its labeling" and cites text on the company's website, which under the Act is considered to be part of the product labelling, as being faulty in this respect. The text says "heart-healthy diets rich in whole grain foods, can reduce the risk of heart disease."

According to the FDA, the claim does not meet the requirements of the Act which requires such assertions to state that "diets low in saturated fat and cholesterol and high in fiber-containing fruit, vegetable, and grain products may reduce the risk of heart disease". The Cheerios labelling neither mentions fruits, vegetables and fiber, nor the need for the diet to be low in saturated fat and cholesterol.

Thus the label does not have enough information to "enable the public to understand the significance of the claim in the context of the total daily diet," said the FDA letter.

The letter also refers to another labelling claim about reduction in cancer risk.

The FDA said the claim, which includes the statement "regular consumption of whole grains as part of, a low-fat diet reduces the risk for some cancers, especially cancers of the stomach and colon", fails to meet the authorized format because, for example, like the other claim, it does not mention fruits and vegetables and fiber content and again denies the public the chance to see the overall context of the healthy diet.

The agency also takes issue with the added phrase "especially cancers of the stomach and colon" which goes beyond what an authorized claim is allowed to say. As the FDA letter explains:

"The claim authorized through the notification procedure does not emphasize the relationship between whole grain foods and stomach and colon cancer as compared to other cancers."

General Mills has 15 days to reply with an explanation of how they intend to "correct the violations" and to ensure that "similar violations do not occur".

Scientists have developed a new approach for surveying phosphorylation, a process that is regulated by critical cell signaling pathways and regulates several key cellular signaling events. The research, published by Cell Press in the April 10th issue of the journal Molecular Cell, describes the regulation of a... previously uncharacterized protein and demonstrates that it plays an important role in cancer cell invasion.

Many cancers, including melanoma, are associated with mutations in the gene encoding the protein kinase B-Raf. Kinases are proteins that regulate the function of other proteins by attaching a phosphate group to them. B-RAF mutations often lead to dysregulation of protein phosphorylation by the mitogen-activated protein (MAP) kinase signaling pathway. Identification and characterization of MAP kinase target proteins is critical for understanding the mechanisms involved in cancer progression.

"In contrast to targets regulated at the level of gene expression, little is known about how proteins are modified in response to oncogenic B-Raf signaling in melanoma cells. In particular, identifying cellular targets for phosphorylation is needed to gain a more comprehensive understanding of the responses to MAP kinase pathway dysregulation in melanoma," explains senior study author Dr. Natalie G. Ahn from the Department of Chemistry and Biochemistry at the University of Colorado and the Howard Hughes Medical Institute.

Current strategies to identify phosphorylated proteins require purification techniques to enrich phosphorylated from non-phosphorylated proteins and metabolic labeling procedures to quantify changes in phosphorylation. Unfortunately, these methods are not readily applied to all sample types. Dr. Ahn and colleagues developed a method for analyzing phosphorylated proteins in human cell extracts that does not depend on enrichment and can be performed quantitatively in a label-free manner.

Using their method, the researchers identified ninety phosphorylation events that were regulated by oncogenic B-Raf. The phosphorylated proteins included many known signaling molecules. However, one of the targets, MINERVA/FAM129B, belonged to a protein family with unknown function. Further investigation established a role for MAP kinase-dependent phosphorylation of MINERVA/FAM129B in cancer cell invasion within a three dimensional extracellular matrix environment.

"Our results revealed successful selection and sequencing of phosphopeptides in proteolytic digests without affinity enrichment, as well as label-free quantitation of regulated protein phosphorylation events," concludes Dr. Ahn. "Further, we demonstrated pathway-dependent phosphorylation of FAM129B and discovered its importance in controlling melanoma cell invasion."

Notes:

The researchers include William M. Old, University of Colorado, Boulder, CO; John B. Shabb, University of North Dakota, Grand Forks, ND; Stephane Houel, University of Colorado, Boulder, CO, Howard Hughes Medical Institute; Hong Wang, University of Colorado, Boulder, CO; Kasey L. Couts, University of Colorado, Boulder, CO; Chia-yu Yen, University of Colorado, Boulder, CO; Elizabeth S. Litman, University of Colorado, Boulder, CO, Howard Hughes Medical Institute; Carrie H. Croy, University of Colorado, Boulder, CO, Howard Hughes Medical Institute; Karen Meyer-Arendt, University of Colorado, Boulder, CO; Jose G. Miranda, University of Colorado, Boulder, CO; Robert A. Brown, University of Colorado, Boulder, CO; Eric S. Witze, University of Colorado, Boulder, CO; Rebecca E. Schweppe, University of Colorado, Boulder, CO; Katheryn A. Resing, University of Colorado, Boulder, CO; and Natalie G. Ahn, University of Colorado, Boulder, CO, Howard Hughes Medical Institute.

Source:
Cathleen Genova
Cell Press

A protein called Mcl-1 plays a critical role in melanoma cell resistance to a form of apoptosis called anoikis, according to research published this week in Molecular Cancer Research.

The presence of Mcl-1 causes cell resistance to anoikis. This resistance to anoikis enables the melanoma cells to metastasize and... survive at sites distant from the primary tumor, according to Andrew Aplin, Ph.D., an associate professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University, and a member of the Kimmel Cancer Center at Jefferson. The research was conducted at Albany Medical College in New York by Dr. Aplin and colleagues.

Mcl-1 is part of the Bcl-2 protein family, and is regulated by B-RAF proteins, which are mutated in approximately 60 percent of all human melanomas. The Bcl-2 family includes several prosurvival proteins that are associated with the resistance of cancer cells to apoptosis, or cell death. Dr. Aplin and colleagues analyzed three candidate Bcl-2 proteins: Mcl-1, Bcl-2 and Bcl-XL.

"When we depleted Mcl-1 from the tumor cells, they were susceptible to cell death," Dr. Aplin said. "Mcl-1 showed dramatic results compared to Bcl-2 and Bcl-XL, which was a surprise. Our findings show that targeting Mcl-1, which is upregulated in a majority of melanoma cells, could be a viable treatment strategy."

Dr. Aplin said there are therapeutic agents in development to target this protein family, but most specifically target Bcl-2 and Bcl-XL. There is one agent in development by Gemin X Biotech that targets Mcl-1. This agent, called obatoclax, is currently in phase I/II trials.

Source: Thomas Jefferson University

People with a family history of the skin cancer melanoma show reductions in anxiety and depression after getting tested for a high-risk gene mutation, reports a study in the May issue of Genetics in Medicine, the official peer-reviewed journal of The American College of Medical Genetics. The journal is published by Lippincott Williams & Wilkins, a part of... Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.

"This study provides preliminary evidence for healthy psychological, behavioral, and cognitive adjustment after participation in genetic testing for melanoma risk," according to lead researcher Nadine A. Kasparian, Ph.D., of University of New South Wales, Australia.

Who Gets Tested, and What Are the Effects?

One hundred nineteen patients were offered testing for mutation of the CDKN2A gene, which has been linked to a very high risk of melanoma. All had a strong family history of melanoma, with at least three affected relatives. A wide range of factors including beliefs about melanoma and genetic testing and symptoms of anxiety and depression were evaluated to assess the characteristics of patients who opted for genetic testing, as well as the impact of being tested.

Over a three-year period, 25 patients decided to be tested. Of these, 75 percent were found to carry the CDKN2A mutation. The researchers had expected that patients with positive test results would have at least a short-term increase in psychological distress.

To the contrary, however, patients who found they carried the high-risk gene had a significant reduction in scores for anxiety at two weeks after testing. Depression scores were also decreased, and remained so at one-year follow-up.

Several factors affected the decision to undergo genetic testing. Patients who believed they were highly susceptible to melanoma were three times more likely to be tested. In contrast, those who believed that melanoma was more likely to be fatal, even if detected early, were about half as likely to be tested. The most frequent reasons for being tested were to aid melanoma research, to learn about melanoma risk in one's children, and to learn about steps to reduce personal risk.

Behavior Changes As Well As Reduced Anxiety

People who tested positive for the high-risk gene became more likely to undergo regular skin examinations by a physician a key part of recommendations for early melanoma detection. Other behaviors, including sunscreen use, were not significantly different for people with positive tests, compared to those who decided not to be tested. Because of the small number of patients with negative gene test results, the impact of testing in this group could not be evaluated.

The genetic factors affecting melanoma risk are complex, but are coming into sharper focus with the discovery of the CDKN2A mutation and other risk genes. Although the CDKN2A test could have important benefits for people with a family history of melanoma, it has yet to come into common clinical use. Benefits of testing could include knowing one's risk and taking preventive steps, such as sun protection and skin examination. The test could also have negative effects, especially psychological distress and "fatalistic" thinking about melanoma.

The encouraging new results suggest that genetic testing for melanoma risk decreases rather than increases anxiety even for patients who discover that they have the high-risk gene. The percentage of patients deciding to be tested is lower than for other genetic tests for disease risk, perhaps because patients question the value of being tested. Dr. Kasparian and coauthors hope their results will lead to "widespread discussion of, and patient education about, the benefits, risks, and limitations" of genetic testing for melanoma risk.

About Genetics in Medicine

Genetics in Medicine is the official peer-reviewed journal of The American College of Medical Genetics. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.

About the American College of Medical Genetics

Founded in 1991, the ACMG provides education, resources and a voice for the medical genetics profession. To make genetic services available to and improve the health of the public, the ACMG promotes the development and implementation of methods to diagnose, treat and prevent genetic disease. Members include biochemical, clinical, cytogenetic, medical and molecular geneticists, genetic counselors, and other health care professionals committed to the practice of medical genetics. Genetics in Medicine, now published monthly, is the official journal of the ACMG.

About Lippincott Williams & Wilkins

Lippincott Williams & Wilkins (LWW) is a leading international publisher for healthcare professionals and students with nearly 300 periodicals and 1,500 books in more than 100 disciplines publishing under the LWW brand, as well as content-based sites and online corporate and customer services. LWW is part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.

Wolters Kluwer Health is a division of Wolters Kluwer, a leading global information services and publishing company. The company provides products and services for professionals in the health, tax, accounting, corporate, financial services, legal, and regulatory sectors. Wolters Kluwer had 2008 annual revenues of €3.4 billion ($4.9 billion), employs approximately 20,000 people worldwide, and maintains operations in over 35 countries across Europe, North America, Asia Pacific, and Latin America. Wolters Kluwer is headquartered in Amsterdam, the Netherlands. Its shares are quoted on Euronext Amsterdam (WKL) and are included in the AEX and Euronext 100 indices.

Source: Wolters Kluwer Health

New genetic research suggests that the traditional risk factors for melanoma may not be as helpful in predicting risk in all people as previously thought, according to data presented at the American Association for Cancer Research 100th Annual Meeting 2009.

"Traditionally, a clinician might look at a person with dark hair who did not sunburn easily and classify them as lower risk for melanoma, but that may not be true for all people in the population," said Peter Kanetsky, Ph.D., M.P.H., assistant professor of epidemiology at the University of Pennsylvania.

Kanetsky and his colleagues have identified that genetic variants in MC1R could help to predict melanoma risk in people who are not usually classified as high risk. While this link previously has been observed, Kanetsky said it is now time to begin discussing genetic factors as part of the overall melanoma risk model.

For the current study, researchers analyzed 779 patients with melanoma from the Pigmented Lesion Clinic of the University of Pennsylvania and compared them with 325 healthy control patients.

Overall, the presence of certain MC1R variants was associated with a more than two-fold risk of melanoma, but this risk was largely confined to those patients who would not usually be considered to be at elevated risk.

Although those with dark hair are not thought to be at increased risk for melanoma, if they had dark hair and also inherited certain MC1R genetic variants, their risk for melanoma increased 2.4-fold. However, no elevated risk was associated with these same MC1R variants in those with blond or red hair.

MC1R was also associated with increased risk among those with dark eye color (3.2-fold increase), who did not freckle (8-fold increase), who tanned after repeated sun exposure (2.4 fold increase) or who tanned immediately without burning (9.5-fold increase). People with these characteristics are usually thought to be at reduced risk for melanoma.

Kanetsky said a clinical screening test for MC1R is not yet available.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and nearly 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes six major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Source: American Association for Cancer Research

The Scottish Intercollegiate Guidelines Network (SIGN) have issued new guidelines for the treatment of stroke, giving clopidogrel (Plavix®) a Grade A recommendation as a monotherapy alternative to the combination of aspirin and dipyridamole in the secondary prevention of vascular events.(1)

New data has been published demonstrating the efficacy of clopidogrel in this indication since the previous guidelines were produced, such as... PRoFESS*, the largest ever trial of its kind in stroke. With the publication of these guidelines, Scotland has again shown itself to be leading the way in terms of using the most recent clinical data to inform the guidance issued for its clinicians.

Under the previous SIGN guidelines, aspirin and dipyridamole was the recommended 1st-line treatment for the secondary prevention of stroke, with clopidogrel only mentioned as a good practice point.(2) The new guidelines recommend that clopidogrel is considered as an alternative to the combination of aspirin and dipyridamole after someone has had a, ischaemic stroke, for the secondary prevention of vascular events. Both treatment options have Grade A status in recognition of the body of clinical evidence supporting their use in this indication.

Chest, Heart & Stroke Scotland Chief Executive David Clark said, "We very much welcome the new guidelines, but we must make sure that the resources are made available to provide these treatments, and that the guidelines are put into practice so that all potential Scottish stroke patients benefit. We also need to improve awareness about the signs and symptoms of a stroke and to drive home the message that stroke is a medical emergency - we are already working with the NHS through our FAST campaign to achieve this."

Stroke is the 3rd largest cause of death and the largest cause of severe disability in Scotland, as it is UK-wide.(3,4) There are an estimated 100,000 stroke survivors currently living in Scotland.(4)

The National Institute for Health and Clinical Excellence (NICE) published their most recent clinical guidelines on stroke in July 2008 (prior to the publication of the PRoFESS data in August) and are currently revising their Technology Appraisal on clopidogrel and dipyridamole for use in vascular disease (expected in 2010).(5)

Clopidogrel has been prescribed for over 10 years in a broad range of atherothrombotic patients, amongst whom it has been shown to provide early and long-term protection against future vascular events. Clopidogrel has a well-known safety and efficacy profile.(6-10)

Notes:

*PRoFESS: Prevention Regimen For Effectively avoiding Second Strokes11

About sanofi-aventis

Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT : SAN) and in New York (NYSE : SNY).

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life.

Plavix® (clopidogrel) is manufactured by sanofi-aventis and Bristol-Myers Squibb.

References:

1 Scottish Intercollegiate Guidelines Network (SIGN), Management of patients with Stroke or TIA: assessment, investigation, immediate management and secondary prevention (SIGN 108) (2008)

2 Scottish Intercollegiate Guidelines Network (SIGN), Management of patients with Stroke: Rehabilitation, Prevention and Management of Complications, and Discharge Planning (SIGN 64) (2002)

3 Department of Health website, http://www.dh.gov.uk/en/healthcare/nationalserviceframeworks/stroke/index.htm (last accessed December 11th 2008)

4 The Stroke Association, http://www.stroke.org.uk/in_your_area/scotland/index.html (last accessed 12th December 2008)

5 National Institute for Health and Clinical Excellence (NICE), Clopidogrel and dipyridamole for the prevention of artherosclerotic events (Technology Appraisal 90). (May 2005)

6 CAPRIE Steering Committee. A randomised, blinded trial of Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE). Lancet 1996; 348: 1329-1339.

7 The Clopidogrel in Unstable angina to prevent Recurrent Events trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. NEJM 2001; 345: 494-502.

8 COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005; 366: 1607-1621.

9 Sabatine MS et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. NEJM 2005; 352: 1179-1189.

10 Yusuf S et al. Early and late effects of clopidogrel in patients with acute coronary syndromes. Circulation 2003; 107: 966-972.

11 PRoFESS Study Group. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. NEJM 2008; 359 1-14

Sources:
Caroline Almeida
Bristol-Myers Squibb

Jeannine Nolan
sanofi-aventis

Abbott (NYSE: ABT) announced two-year data from 30 patients in its ABSORB clinical trial, demonstrating that its bioabsorbable drug eluting stent successfully treated coronary artery disease and was absorbed into the walls of treated arteries within two years, leaving behind blood vessels that appeared to move and function similar to unstented arteries. Patients who received Abbott's bioabsorbable drug eluting coronary stent and... were followed out to two years experienced no stent thrombosis out to two years and no new major adverse cardiac events (MACE) between six months and two years. These results confirmed earlier positive one-year clinical results with Abbott's bioabsorbable drug eluting stent. The results were presented today at the Cardiovascular Research Foundation's 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium.

"Now you see it, now you don't -- for the first time, we have data in patients showing that Abbott's bioabsorbable drug eluting stent does its job treating diseased coronary arteries and that it is absorbed by two years," said John Ormiston, M.D., principal investigator in the ABSORB trial and medical director at Mercy Angiography in Auckland, New Zealand. "Clinical safety and effectiveness were sustained at two years, and the previously stented portion of arteries demonstrated the ability to expand and contract in a manner similar to a vessel that has never been stented. These are very exciting results that represent a potential major breakthrough in the future treatment of patients with coronary artery disease."

Trends were observed in data from tests of artery movement and function, demonstrating a potential restoration of unstented artery movement to coronary blood vessels after the stent was absorbed -- something that is not possible with permanent metal-based stent implants.

Abbott also will present groundbreaking intravascular ultrasound (IVUS) and optical computed tomography (OCT) imaging data on its bioabsorbable drug eluting coronary stent platform this week at TCT in the "Best of Coronary Interventions Abstracts" session at 9:20 a.m. Eastern time on Wednesday, Oct. 15, 2008. IVUS data will reveal a decrease in plaque area in treated arteries corresponding to a similar increase in blood flow area between six months and two years: 12.7 percent decrease in plaque area (p=<0.001, n=17); 10.8 percent increase in luminal area (p=0.03, n=17). OCT imaging data will show absorption of the stent into artery walls and that the blood vessel lining of arteries treated with Abbott's bioabsorbable stent looks more uniform after two years than it did immediately post-treatment.

"The imaging technology data from the ABSORB trial indicate that Abbott's bioabsorbable stent has the potential to restore vascular integrity and endothelial function to treated vessels after two years," said Professor Patrick W. Serruys, M.D., Ph.D., professor of interventional cardiology at the Thoraxcentre, Erasmus University Hospital, Rotterdam, and co-principal investigator in the ABSORB trial. "With these ABSORB data, we have come full circle in interventional time, linking the past, when balloon angioplasty was used without stents, to the future, when disappearing stents may become the new standard of care for patients with coronary artery disease."

Abbott is the only company with long-term clinical data evaluating the safety and performance of a fully bioabsorbable drug eluting coronary stent out to two years. Abbott's bioabsorbable everolimus eluting coronary stent is made of polylactic acid, a proven biocompatible material that is commonly used in medical implants such as dissolvable sutures. As with a metallic stent, Abbott's bioabsorbable stent is designed to restore blood flow by propping a clogged vessel open, and to provide support until the blood vessel heals. Unlike a metallic stent, however, a bioabsorbable stent is designed to be slowly metabolized by the body and completely absorbed over time.

"The early success of our bioabsorbable stent marks the dawn of the beginning of a new era in the history of interventional medical device treatment," said John M. Capek, Ph.D., executive vice president, Medical Devices, Abbott. "Today's data show that bioabsorbable stents have become more than just a wish for patients -- they are now on their way to becoming a clinical reality."

Abbott will begin enrolling the next cohort of 80 patients into its international ABSORB clinical trial in the first half of 2009.

ABSORB Clinical Trial Results

Two-year data from the first 30 patients enrolled in the ABSORB clinical trial demonstrated a low (3.6 percent, n=28) MACE rate, which was consistent with results at one year (3.4 percent, n=29) and before six-months (3.3 percent, n=30). One patient had a minor heart attack due to lack of blood supply at six-months, another was electively lost to follow up at one year, and one patient died from a non-cardiac cause at two years. A zero percent stent thrombosis rate persisted for all patients across all time points in the ABSORB trial. Potential restoration of unstented artery movement to coronary blood vessels after the bioabsorbable stent was absorbed was revealed at two years with the drugs acetylcholine and nitroglycerin used in nine patients, showing vasodilation in the previously stented area, and methergine used in seven patients, showing vasoconstriction in the previously stented area.

About the ABSORB Clinical Trial

The ABSORB trial is a prospective, non-randomized (open label) study designed to enroll up to 110 patients in Belgium, Denmark, France, New Zealand, Poland and the Netherlands. Key endpoints of the study include assessments of safety -- MACE (defined as any event that resulted in re-treatment of the treated artery, heart attack or cardiac death) and stent thrombosis (blood clot formation) rates -- at 30, 180 and 270 days, with additional annual follow-up for up to five years, as well as an assessment of the acute performance of the bioabsorbable drug eluting stent. Other key endpoints of the study include successful deployment of the bioabsorbable drug eluting stent, follow-up measurements assessed by angiography, intravascular ultrasound (IVUS), and state-of-the-art imaging modalities at 180 days and two years.

Everolimus, developed by Novartis Pharma AG, is a proliferation signal inhibitor, or mTOR inhibitor, licensed to Abbott by Novartis for use on its drug eluting stents. Everolimus has been shown to inhibit in-stent neointimal growth in the coronary vessels following stent implantation, due to its anti-proliferative properties.

For images of Abbott's bioabsorbable stent and other information, please visit the company's online TCT newsroom at http://www.abbottvascular.com/presskit.

About Abbott Vascular

Abbott Vascular, a division of Abbott, is one of the world's leading vascular care businesses. Abbott Vascular is uniquely focused on advancing the treatment of vascular disease and improving patient care by combining the latest medical device innovations with world-class pharmaceuticals, investing in research and development, and advancing medicine through training and education. Headquartered in Northern California, Abbott Vascular offers a comprehensive portfolio of vessel closure, endovascular and coronary products.

About Abbott

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 68,000 people and markets its products in more than 130 countries.

Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com.

Abbott

Antiplatelet medicine, AGGRASTAT® (tirofiban HCL), a glycoprotein IIb/IIIa inhibitor, has been shown to significantly lower the incidence of heart attack after elective coronary angioplasty, in patients with coronary artery disease who have shown poor response to standard oral antiplatelet agents such as... aspirin and clopidogrel.1 These results were announced at the Annual European Society of Cardiology Congress in Munich, Germany.

"These findings are significant in that we demonstrate a proof of concept for a new treatment strategy in a patient segment whose needs have so far remained unaddressed - managing for the increased risk of thrombotic events due to non-responsiveness of patients to standard oral antiplatelets such as aspirin or clopidogrel," said Dr Marco Valgimigli, Chair of Cardiology, University of Ferrara, Italy and principal investigator of the 3T/2R Study (Tailoring Treatment with Tirofiban in patients showing Resistance to aspirin and/or Resistance to clopidogrel).

Inhibition of platelet aggregation following an intake of aspirin or clopidogrel varies greatly among patients, and previous studies have shown that poor response to oral antiplatelet agents increases the risk of thrombotic events, especially after coronary angioplasty.1 It was previously unknown if this reflected suboptimal platelet inhibition per se which might benefit from alternative or more potent antiplatelet agents.

Enrolled in the study were 263 patients who were poor responders to aspirin and/or clopidogrel, based upon a point-of-care assay, who underwent elective coronary angioplasty at ten European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double blind manner to receive either AGGRASTAT® or placebo on top of standard aspirin and clopidogrel therapy.1 The primary end point was the occurrence of periprocedural myocardial infarction, as defined by an increase in Troponin I or T within 48 hours, and was observed in 20.4 percent of patients treated with AGGRASTAT®, compared to 35.1 percent of patient treated with placebo.1 This resulted in a significant reduction of major adverse cardiovascular events within 30 days in the AGGRASTAT® group compared to the placebo group (21.2 percent versus 36.6 percent, respectively; p=0.0065).1 The incidence of bleeding was low and did not differ between the two groups.1

"Current treatment strategies for patients with coronary artery disease ignore the individual response to antiplatelet agents, and likewise fail to identify therapeutic targets for platelet reactivity necessary to intensify treatment," said Dr Paul Gurbel, Director of Cardiovascular Research, Centre for Thrombosis Research, Sinai Hospital, Baltimore, USA. "These findings illustrate the efficacy and safety of AGGRASTAT® in treating poor responders to aspirin or clopidogrel, as compared to standard care. This study shows that by assessing response to standard antiplatelet agents by a point-of-care assay, intensity of treatment can be modulated accordingly."

Dr Gurbel further commented, "These data are in accordance with our earlier results from the CLEAR PLATELETS studies that have demonstrated the strong association between high periprocedural platelet reactivity and the risk of in-hospital myocardial infarction in patients undergoing elective stenting. The use of glycoprotein IIb/IIIa inhibitors, in patients identified as poor responders to oral antiplatelet agents by objective measurements of platelet function, makes perfect sense and deserves greater attention in future studies."

"These data findings are extremely encouraging for this patient population and we believe it reinforces the potential benefits of high-dose bolus AGGRASTAT®," said John Vavricka, President and Chief Executive Officer of Iroko Pharmaceuticals. "Iroko is committed to furthering clinical research in this area, and exploring AGGRASTAT®'s potential for patients who do not respond to oral anti-platelet therapy."

In January of 2008, Iroko Pharmaceuticals acquired all non-US commercial rights to AGGRASTAT® from Merck & Co., Inc. The 3T/2R study was initiated and conducted by the University of Ferrara, Italy with an unrestricted grant from Merck & Co., Inc. and Iroko.

About AGGRASTAT®

AGGRASTAT®, a glycoprotein IIb/IIIa inhibitor, is indicated for the prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction with the last episode of chest pain occurring within 12 hours and with ECG changes and/or elevated cardiac enzymes. Patients most likely to benefit from AGGRASTAT® treatment are those at high risk of developing myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early PTCA.

In most patients, AGGRASTAT® should be administered intravenously, at an initial rate of 0.4 mcg/kg/min for 30 minutes and then continued at 0.1 mcg/kg/min. For complete information, please refer to the product's prescribing information. AGGRASTAT® is intended for use with acetylsalicylic acid and unfractionated heparin.

AGGRASTAT® (tirofiban hydrochloride) is contraindicated in patients with known hypersensitivity to any component of the product; active internal bleeding or a history of bleeding diathesis within the previous 30 days; or a history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Other contraindications to AGGRASTAT® include: a history of thrombocytopenia following prior exposure to AGGRASTAT®; history of stroke within 30 days or any history of hemorrhagic stroke; major surgical procedure or severe physical trauma within the previous month; or history, symptoms, or findings suggestive of aortic dissection. AGGRASTAT® is also contraindicated in patients with: severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg); concomitant use of another parenteral GP IIb/IIIa inhibitor; or acute pericarditis.

Bleeding is the most common complication encountered during therapy with AGGRASTAT®. Administration of AGGRASTAT® is associated with an increase in bleeding events classified as both major and minor bleeding events, by criteria developed by the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding associated with AGGRASTAT® occurs at the arterial access site for cardiac catheterization. Fatal bleedings have been reported. AGGRASTAT® should be used with caution in patients with platelet count <150,000/mm3, in patients with hemorrhagic retinopathy, and in chronic hemodialysis patients. Because AGGRASTAT® inhibits platelet aggregation; caution should be employed when it is used with other drugs that affect hemostasis. The safety of AGGRASTAT® when used in combination with thrombolytic agents has not been established. During therapy with AGGRASTAT®, patients should be monitored for potential bleeding. When bleeding cannot be controlled with pressure, infusion of AGGRASTAT® and heparin should be discontinued.

The following additional adverse reactions have been reported in post- marketing experience: bleeding, intracranial bleeding, retroperitoneal bleeding, hemopericardium, and pulmonary (alveolar) hemorrhage. Fatal bleedings have been reported; body as a whole: acute and/or severe decreases in platelet counts which may be associated with chills, low grade fever, or bleeding complications; hypersensitivity; rash and/or hives.

Please refer to the specific Prescribing Information for your country for complete warnings and precautions.

About Iroko

Iroko is a pharmaceutical company focused on acquiring, developing, and maximizing the potential of currently marketed pharmaceutical products on a worldwide basis. Iroko applies concentrated selling and marketing efforts and product life cycle management strategies focused on developing new and relevant formulations and indications that benefit patient health. For more information, visit http://www.iroko.com.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. http://www.merck.com

References

1 Valgimigli M, Campo Gianluca, de Cesare N, Meliga E et al. A double-blind randomised multicentre trial of tailored infusion of tirofiban in poor aspirin and/or clopidogrel responders undergoing elective percutaneous coronary intervention. Presented at ESC, 2 September 2008

Merck & Co., Inc

Four studies published in a leading journal this week suggest that metabolic disorders such as obesity and diabetes may share risk factors that affect the development of Alzheimer's disease, other forms of dementia and cognitive decline.

The studies are published in the March issue of Archives of Neurology, a JAMA/Archives journal and find that:...

1. The more components of metabolic syndrome a woman has, the more likely she is to develop cognitive impairment
Dr Kristine Yaffe of the University of California, San Francisco, and the San Francisco Veterans' Affairs Medical Center, and colleagues recruited nearly 5,000 women of average age 66 with no cognitive impairment and followed them for four years. Of the 10 per cent who had metabolic syndrome, 7 per cent developed cognitive impairment compared with 4 per cent who did not have metabolic syndrome. The risk of developing cognitive impairment went up for each additional metabolic syndrome component present. (Click here for more info).

2. A man who is obese in old age is more likely to have worse cognitive function
Dr Alka M Kanaya of the University of California-San Francisco, and colleagues studied over 3,000 elderly people enrolled in the Health ABC Study. They assessed their overall body fat (adiposity) from their their body mass index, waist size, saggital diameter (from highest point of abdomen to the back), total fat, subcutaneous fat (under the skin) and visceral fat (between internal organs). Men with higher levels of body fat performed worse in cognitive function tests taken at the beginning of the study and after three, five and eight years. But no such link was found in the women.(Click here for more info).

3. Being obese in middle age, or underweight in old age puts a person at greater risk of dementia
Dr Annette L Fitzpatrick of the University of Washington, Seattle, and colleagues followed 2,700 adults of average age 75 without dementia who reported their weight in midlife (age 50) and had their height and weight measured in late life (age 65 and over). The average follow up was 5.4 years. They found that those people who were obese in midlife (body mass index, BMI, over 30) were more likely to develop dementia than those of normal weight. However, in late life the picture was quite different. Being obese in late life appeared to protect against dementia, while being underweight (BMI under 20) put a person at increased risk, and being overweight had no effect. (Click here for more info).

4. A person with Alzheimer's disease who has a history of diabetes and higher levels of total and "bad" (LDL) cholesterol is more likely to have a faster rate of cognitive decline
Dr Elizabeth P Helzner and colleagues at the Columbia University Medical Center, New York, studied 156 patients who were diagnosed with Alzheimer's at average age 83 and followed them for an average of 3.5 years. Over this time, those with higher LDL ("bad" cholesterol) and total cholesterol before diagnosis showed a faster decline on tests of cognitive function compared to those whose cholesterol was normal. This was the same for those who had a history of diabetes compared to those who did not. (Click here for more info).

Metabolic syndrome is a group of risk factors that predisposes a person to heart disease, diabetes, and other conditions. The risk factors include: obesity, mild glucose abnormalities, high blood pressure, and adverse changes in blood fats.

Metabolic syndrome affects about one in five people and older people more. Some studies suggest 1 in 4 people in the US have the condition.

In an accompanying review titled " Insulin Resistance May Links Metabolic and Cognitive Disorders", Dr Suzanne Craft of Veterans Administration Puget Sound Health Care System and University of Washington School of Medicine in Seattle, suggested that insulin resistance, which is when the tissues in the body stop being sensitive to the hormone that controls glucose levels, may be behind dementia and metabolic disorders like diabetes and obesity.

Craft wrote:

"Considerable progress has been made in establishing relationships among metabolic disorders and late-life dementing illnesses."

"A number of challenges must be addressed as we move forward to determine the key mechanisms underlying these associations," she concluded, while emphasizing the need to have clear definitions of both metabolic and neurological conditions.

"Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of late-life dementias, but will also inspire novel strategies for treating and preventing these disorders," wrote Craft.

Sources: JAMA/Archives.

WHAT:

Women with suspected coronary artery disease who suffer from depression have significantly higher health care costs than those who are not depressed, according to findings from the Women's Ischemia Syndrome Evaluation (WISE), an ongoing, multicenter study funded by the National Institutes of Health.

Previous studies have shown that patients suffering from certain medical conditions and depression have greater health expenses than... those without depression. Because women are diagnosed with depression at twice the rate of men, the study of costs related to depression and women's health issues is particularly important.

WHO:

C. Noel Bairey Merz, M.D., is available to provide additional details. She is one of the journal article authors and chair of the multicenter WISE initiative, which is investigating potential methods for more effective diagnosis and evaluation of coronary artery disease in women. Bairey-Merz serves as director of the Women's Heart Center at the Cedars-Sinai Heart Institute, where she also directs the Preventive and Rehabilitative Cardiac Center at the Cedars-Sinai Heart Institute. A professor of medicine at Cedars-Sinai Medical Center, she holds the Women's Guild Endowed Chair in Women's Health.

DETAILS:

This study, conducted among 868 women undergoing evaluations for possible coronary artery disease, used three different approaches to measure depression (history of treatment for depression, use of antidepressant medications, and a standard, widely accepted questionnaire). Seventeen percent to 45 percent of the women in the study met depression criteria.

Depression was associated with 15 percent to 53 percent increases in cardiovascular costs over five years. Translated into dollar figures, annual cardiovascular costs were $1,550 to $3,300 higher for depressed women than for those who were not depressed (depending on the depression criteria used).

Several factors appear to be responsible for these increased costs, but one clear association is the fact that the depressed women experienced more cardiovascular disease events. Interestingly, relationships between depression and costs were particularly strong among women who did not have evidence of significant coronary artery disease, suggesting that depression may play a larger cost role in women who do not have traditional markers of heart disease. These results combined with prior work suggest that women with symptoms of heart disease without obstructive CAD are more prone to depression possibly secondary to misdiagnosis and misunderstanding. More research is needed," said Bairey Merz.

RAMIFICATIONS:

The findings suggest that depression is an important factor in understanding overall and cardiovascular-related costs in women who have symptoms of heart disease. Although it is not currently known whether treatment for depression can lower costs in cardiac populations, the results support future research in this area.

FUNDING:

The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, the National Center for Research Resources, the Gustavus and Louis Pfeiffer Research Foundation, The Women's Guild of Cedars-Sinai Medical Center, The Ladies Hospital Aid Society of Western Pennsylvania, and the Edythe Broad Endowment for Women's Heart Research.

Notes:

The study abstract can be accessed

Evalve, Inc., the leader in the development of devices for the percutaneous repair of cardiac valves, announced that the first series of patients have been successfully treated with the MitraClip(R) system at the Cardiocentro Ticino in Lugano, Switzerland. The MitraClip(R) system is the only medical device commercially available in the European Union which provides a non-surgical mitral valve repair option for... patients suffering from the effects of functional and degenerative mitral regurgitation (MR).

Mitral regurgitation is the most common type of heart valve insufficiency in Europe and the United States, affecting millions of people worldwide. In the vast majority of patients, the MR is untreated, requiring the heart to work harder and ultimately leading to heart failure.

The first patients in Switzerland were treated by the team led by Prof. T. Moccetti, M.D., assisted by G.B. Pedrazzini, M.D.; E. Pasotti, M.D.; F.F. Faletra, M.D.; and A. Auricchio, M.D., Ph.D.

"Until now, many heart failure patients with associated functional MR had no therapeutic options except medical management when surgery was not possible either because they have already had heart surgery, or presented with important renal insufficiency or lung disease, all of which significantly increase the risk of a second or a third operation," said Prof. Moccetti, Head of Cardiology Division and Medical Director of Cardiocentro Ticino. He added "The MitraClip(R) therapy provides a valuable alternative for these patients."

Professor Auricchio, Director of the Heart Failure Clinic commented: "Heart failure is a devastating disease, significantly more common than cancer and has the same poor life-expectancy. Implantable devices such as cardiac resynchronization therapy have improved the quality of life of these patients. Now with percutaneous mitral valve repair, I am confident we can expand our treatment possibilities to many of our Swiss heart failure patients."

Evalve initiated commercial sales of the MitraClip(R) system in Europe under the CE Mark in September 2008. The company is employing a direct sales strategy and is taking a disciplined and measured approach to the initial commercial roll out. The company has worked closely with hospitals to deliver high quality training programs in preparation for the first series of implants. The MitraClip(R) device is now currently being implanted in five countries, including Germany, Italy, the United Kingdom, the Netherlands and now Switzerland.

"We are very pleased to see the successful initial use of the MitraClip device in Switzerland at this important cardiac center," said Ferolyn Powell, president and chief executive officer of Evalve. "The functional MR heart failure patient continues to be the fastest growing segment of the population undergoing treatment with the MitraClip(R) system and the initial commercial results in this population are very encouraging."

About the MitraClip(R) Procedure

Percutaneous mitral repair with Evalve's MitraClip(R) device is performed by physicians in the catheterization laboratory. The heart beats normally during the procedure, and therefore does not require a heart-lung bypass machine. In addition to improving blood flow through the heart, the procedure may also relieve symptoms such as fatigue and shortness of breath that often affect patients with significant MR. After treatment, patients generally recover quickly. The MitraClip(R) device may improve quality of life and may help MR patients avoid or delay surgery, having preserved surgical options (valve repair or replacement) should surgery become necessary.

About Evalve, Inc.

Founded in 1999, Evalve, Inc., headquartered in Menlo Park, Calif., has developed a proprietary system which enables percutaneous repair of cardiac valves. The company's initial products are intended to reduce the risks, trauma and costs associated with current open, arrested heart surgical options. For more information about Evalve, Inc., and for an animated explanation of the procedure using the MitraClip(R) device, visit http://www.evalveinc.com. Evalve is the first portfolio company from the medical device company incubator, The Foundry (http://www.thefoundry.com).

The MitraClip(R) system is currently undergoing clinical evaluation in the United States and Canada.

MitraClip(R) and Evalve are registered trademarks of Evalve, Inc.

Evalve, Inc.

A heart surgeon and a cardiologist specializing in electrophysiology have collaborated to perform the nation's first-ever Convergent Ex-Maze procedure to correct atrial fibrillation at FirstHealth Moore Regional Hospital. Atrial fibrillation, or afib, is an often debilitating heart disorder that... affects an estimated five million Americans.

Cardiothoracic surgeon Andy C. Kiser, M.D., who led the development of the Ex-Maze procedure for atrial fibrillation, and electrophysiologist Mark Landers, M.D., combined their expertise to perform the groundbreaking Convergent Ex-Maze on Jan. 23, 2009. Each physician had performed his specialty (the Ex-Maze by Dr. Kiser and the percutaneous endocardial catheter ablation by Dr. Landers) separately numerous times before, but never together until the January collaboration.

"This case is significant because we can now treat atrial fibrillation without chest incisions and because by working with the electrophysiologist during the procedure, we can do a complete atrial fibrillation treatment," Dr. Kiser says.

"The power of this new procedure is that we have heart surgeons and cardiologists taking tried-and-true technologies and working together to provide the best option for the treatment of atrial fibrillation," says Dr. Landers.

Atrial fibrillation (afib), which affects an estimated five million people, is the most common type of heart rhythm disturbance. It is the rapid, uncoordinated beating of the atria in the two upper chambers of the heart. With afib, the atria quiver instead of beating in rhythm when the electrical impulses that cause them to contract travel through the heart in chaotic fashion.

There are three types of atrial fibrillation: paroxysmal, persistent and long-standing persistent. Paroxysmal afib occurs when the abnormal electrical signals and rapid heart rate begin suddenly and then stop on their own. Symptoms can be mild or severe and last for seconds, minutes, hours or days. With persistent afib, the abnormal heart rhythm continues until it is stopped with treatment. Long-standing persistent afib lasts for more than one year. Both paroxysmal and persistent atrial fibrillation may become more frequent and eventually result in a long-standing or permanent afib.

Some people with afib are severely debilitated by weakness, shortness of breath or pain while others have no symptoms at all.

The union of the Ex-Maze procedure and catheter ablation provides many benefits to the patient including:

Elimination of chest incisions
Quicker recovery time
Shorter hospital stay
Minimal scarring
Ablation testing at the time of the Ex-Maze to confirm appropriate treatment endpoints

During the Convergent Ex-Maze procedure, the Ex-Maze portion is performed through a small incision in the abdomen while a small catheter is inserted in the large vein in the groin for the catheter ablation.

"This eliminates the need for sometimes painful incisions in the chest and allows instantaneous confirmation of the success of the procedure," says Dr. Kiser. "This approach allows the patient to have a quicker recovery and also allows us to add new lesions to parts of the heart that we couldn't reach before. In addition, it allows patients who travel from great distances for the treatment to be able to fly to the area instead of having to drive."

Dr. Kiser recently traveled to the Texas Cardiac Arrhythmia Institute at St. David's Medical Center in Austin, Texas, to observe Rodney Horton, M.D., an electrophysiologist, and Andrew Hume, M.D., a cardiac surgeon, perform the second procedure in the United States. Andrea Natale, M.D., medical director of the heart arrhythmia program at St. David's and an internationally known heart arrhythmia specialist, was also on hand for the procedure.

Various improvements to the traditional open-heart surgery technique have been developed to block the stray electrical impulses of atrial fibrillation and guide electricity onto the correct pathways through the heart. Other traditional treatments include medication, pacemaker implantation and electrical shock, all of which are offered at Moore Regional Hospital.

For many years, the "gold standard" for afib treatment has been a surgical procedure called the Cox Maze, which requires opening the chest, stopping the heart and cutting it into sections before it is sewn back together. Dr. Kiser's Ex-Maze procedure, a novel improvement to the Cox Maze that he developed in collaboration with other surgeons, creates an extensive pattern of scar tissue on the heart's surface and controls the heart's abnormal electrical impulses without the complexity of similar procedures.

"A major advantage of the Ex-Maze is that the procedure is done while the heart is beating, so the patient doesn't have to be on a heart-lung machine," Dr. Kiser says.

Initially, Dr. Kiser performed the Ex-Maze only on patients who were having some other type of open-chest procedure, such as a coronary artery bypass. In 2007, he was invited to Krakow, Poland, where he performed the world's first minimally invasive Ex-Maze procedure using Paracardioscopy, which allows surgeons to look at and operate on the heart by using ports and small cameras. He began offering the Paracardioscopic Ex-Maze as a treatment option at Moore Regional in January 2008.

Catheter ablation, a common medical procedure to treat atrial fibrillation, uses a long, thin, flexible tube (called an ablation catheter) that is typically put into a blood vessel in the arm, groin (upper thigh) or neck. The tube is guided to the heart through the blood vessel, and a special machine sends energy through the catheter to the heart. This energy finds and destroys small areas of heart tissue where abnormal heartbeats may cause an arrhythmia to start. During the Convergent Ex-Maze procedure, the ablation catheter is inserted into the heart through the groin.

The Convergent Ex-Maze can be used to treat all three types of atrial fibrillation, but focuses on those patients who have been difficult to treat with traditional methods.

"Those difficult-to-treat patients, who have had atrial fibrillation for a long time, are the patients we are now treating with this procedure," says Dr. Kiser.

Dr. Kiser is a member of the Cardiovascular and Thoracic Center and chief of Thoracic Surgery at Moore Regional Hospital. Also, the medical director of FirstHealth's Chest Center of the Carolinas and Arrhythmia Center, he has been performing heart and lung surgeries at Moore Regional since 2000 and has performed more than 150 minimally invasive Ex-Maze procedures.

Dr. Landers is affiliated with Pinehurst Cardiology Consultants, a comprehensive cardiology practice in Pinehurst.

For more information on the Convergent Ex-Maze atrial fibrillation procedure developed by Dr. Andy Kiser and Dr. Mark Landers, please contact FirstHealth Moore Regional Hospital at (800) 213-3284 or visit http://www.firsthealth.org/afib. Additional information is also available on the Ex-Maze Web site at http://www.exmaze.com.

CUTLINE

A team of American and Polish physicians performed the world's first Convergent Ex-Maze procedure in Krakow, Poland, in January 2009. Members of that team are (front from left) Rodney Horton, M.D., an electrophysiologist with St. David's Medical Center in Austin, Texas; Andy Kiser, M.D., the Moore Regional Hospital cardiac surgeon who developed the groundbreaking procedure; and Andrew Hume, M.D., a cardiac surgeon with St. David's Medical Center in Austin, Texas; and (back from left) David Haines, M.D., a cardiologist with William Beaumont Hospital in Michigan; and cardiac surgeon Krzysztof Bartus, M.D., of Poland. Source medical update

K2M, Inc., a spinal device company developing innovative solutions for the treatment of complex spinal pathologies, announced the introduction of an all-inclusive solution for rigid posterior fixation of the cervico-thoracic regions of the spine. The CASPIAN™ Spinal System has received FDA 510(k) and CE Mark clearance for... domestic and international distribution, expanding the global presence of K2M technologies.

This comprehensive system provides two different polyaxial screw options, Mini MESA™ and Mini DENALI™, as well as Mini Hooks and 3.5 mm Rods. The Mini MESA screws feature K2M's flagship Zero-Torque Technology™ which applies zero torsional loads, or twisting forces, to the spine when locking the system. The Mini DENALI screws feature off-axis screw height adjustment, whereby the screwdriver does not need to be co-linear with the screw shaft to adjust the screw during surgery.

According to Dr. Pierce Nunley, Director of the Spine Institute of Louisiana, "The Zero-Torque locking mechanism and ability to do complex manipulations easily on individual screws across multi-level constructs is superior to any other posterior cervico-thoracic reconstruction system on the market."

"The CASPIAN Spinal System is an important introduction for K2M, because it addresses the increasing demand from the surgeon community to offer our innovative MESA Zero-Torque Technology for the upper regions of the spine," stated Eric Major, K2M's President and CEO. "The CASPIAN clearance moves us one step closer to our goal of providing a complete product portfolio of best-in-class systems for treating all types of complex spine pathologies."

About K2M

K2M, Inc. is an innovative spinal device company that develops simplified solutions for the treatment of complex spinal pathologies and procedures. Chief Medical Officer, Chairman and co-founder, Dr. John Kostuik, former Chief of Spine Surgery at The Johns Hopkins University School of Medicine, drives K2M's commitment to redefining the market. K2M's comprehensive line of products include: spinal stabilization systems, minimally invasive systems, and other advancements in spine solutions for Degenerative Disc Disease (DDD), as well as deformity, trauma, and tumor.

K2M, Inc