Stroke Pilot Study Results To Be Announced At University Of Leicester, UK
April 3, 2008
Preliminary results from a major multi-centre UK pilot trial into Stroke are to be announced at the University of Leicester on 22 April.
Stroke is the third highest cause of death in the United Kingdom, and the single biggest cause of adult disability, with over 300,000 individuals living in the UK with moderate or severe stroke related disability.
People from South Asian groups are potentially at higher risk of suffering from a stroke, and this is particularly important locally given the make up of Leicester’s population.
Findings from research co-ordinated at the University of Leicester will be discussed at an inaugural lecture given by Professor Tom Robinson, Professor of Stroke Medicine, Department of Cardiovascular Sciences, University of Leicester.
The lecture, Time is Brain: to treat BP or not - is that the only question?, will be held on Tuesday 22nd April 2008 at 5.30pm in the Ken Edwards Building, Lecture Theatre 1. It is open and free to the public.
Professor Robinson said: “The Department of Health has recently invested substantial monies into research infrastructure for stroke in England, and the University of Leicester and the University Hospitals of Leicester NHS Trust co-host the Trent Stroke Research Network, comprising centres in Barnsley, Doncaster, Rotherham, Sheffield, Derby, Nottingham, Chesterfield, Mansfield, Lincoln, Kettering and Northampton, as well as the co-ordinating centre in Leicester.
“I am Director of the Trent Stroke Research Network and I will discuss the importance of the Stroke Research Network for future acute treatment, rehabilitation and prevention of stroke, with examples of ongoing clinical trials.”
In particular, Professor Robinson will consider two major multi-centre United Kingdom Trials co-ordinated by the Department of Cardiovascular Sciences in the University of Leicester. The ‘Controlling Hypertension and Hypotension Immediately Post-stroke Trial’ has recently completed its pilot phase, and preliminary results will be discussed. Together with the ongoing ‘Continuing Or Stop post-Stroke Anti-hypertensives Collaborative Study’, these trials focus on an important clinical management dilemma, namely the treatment of high blood pressure in the acute phases of stroke. Blood pressure management, together with associated disturbances in cardiovascular autonomic control, have been a long term research interest of the Department of Cardiovascular Sciences, and Professor Robinson’s lecture will highlight the significant contribution that past and ongoing research in Leicester has helped in answering these questions.
University of Leicester
Vascular Checks Will Prevent Thousands Of Heart Attacks And Strokes
April 2, 2008
Everyone aged between 40 - 74 offered checks
A national programme to identify vulnerability to vascular diseases will prevent up to 9,500 heart attacks and strokes every year and save 2,000 lives, Health Secretary Alan Johnson announced.
Collectively, vascular diseases - heart disease, stroke, diabetes and kidney disease - affect the lives of more than four million people and kill 170,000 every year. They also account for more than half the mortality gap between rich and poor.
Initial results from modelling work carried out by the Department shows that a vascular check programme would prevent 4,000 people a year from developing diabetes. It could also detect at least 25,000 cases of diabetes or kidney disease earlier, allowing cases to be better managed and improving outcomes.
Alan Johnson said:
“As we look to the future of the NHS in its 60th anniversary year, our vision is to create a modern service that meets the unique challenges of today’s society.
“The case for a national programme of vascular checks is compelling. We could prevent 9,500 heart attacks and strokes every year and save 2,000 lives. It would also reduce the health inequalities that blight the lives of the country’s most deprived families.
“The NHS is becoming more personal and responsive to individual needs; becoming as good at prevention and keeping people healthy as it is at providing care and cures; and able to offer the information and support people need to make healthy choices.
“This is an NHS that is properly equipped to face the challenges of the next 60 years.”
We are today setting out our evidence for a national vascular check programme in Putting Prevention First. Everyone between the ages of 40 and 74 will be entitled to the checks.
The checks would be based on straightforward questions and measurements such as age, sex, family history, height, weight and blood pressure. They would also include a simple blood test to measure cholesterol.
Everyone would receive a personal assessment report, setting out not only the person’s level of risk, but exactly what they could do to reduce it. For those at low risk, this might be no more than general advice on how best to stay healthy. Others may be assisted to join a weight management programme or a stop smoking service. Those at the highest risk might also require preventative medication with statins or blood pressure treatment.
Associate Chief Medical Officer Bill Kirkup said:
“We aim to make vascular checks to be available in a variety of convenient places. These could include GP surgeries, pharmacies or other community settings. This programme can make a major contribution to preventing early death and disability, and it is vital that it reaches as many people as possible.
“We are also determined to tackle the inequalities in health, and vascular diseases are the main cause. All too often, people with the worst health have the poorest access to GPs. We want a system that will encourage them to take part, and help to reduce the health gap between rich and poor.”
We intend to begin implementation in 2009/10. We will now work with our key partners across the NHS, the medical profession and the voluntary sectors in drawing up a national system that works for them and patients.
Our initial modelling suggests that the annual costs will be in the region of ￡250 million per year. This includes the cost of the checks themselves as well as the NHS care likely to result from the checks once the proposals are fully implemented across the NHS. However, these figures depend on the details of implementation and levels of demand. We will refine these costings as we continue to design an implementation system with our partners.
We have put aside resources from the health budget and we are committed to providing this funding to the NHS to support this critical shift towards prevention.
Anne Mackie, Director of the UK National Screening Committee, said:
“The UK National Screening Committee welcomes the priority that the government has placed on implementing its recommendations in England. We will now work with stakeholders and the public to develop robust implementation plans. We will particularly focus on how we can make this accessible to the whole population and reduce inequalities in vascular health.”
The Department also announced today the extension of a scheme to help patients on low incomes with the costs of travelling to health care appointments. Currently, patients on low incomes and in receipt of certain means-tested benefits are eligible for help in meeting the costs of travelling to receive hospital-based treatment. This follows referral by a consultant as part of the Hospital Travel Costs Scheme.
As health care services are increasingly delivered outside of hospitals, financial help toward travel costs will, from today, be available to all patients who meet the criteria and are referred by doctors and dentists for traditionally hospital-based treatments wherever these are carried out. To reflect this change, the scheme is being renamed as the Healthcare Travel Costs Scheme.
The expanded travel costs scheme means that patients will be able to choose where they access the healthcare that best suits their needs without having to worry about the travel costs involved.
Notes
1. Copies of Putting Prevention First are available on the DH website: http://www.dh.gov.uk
2. In January, the Prime Minister announced our intention to bring forward new check-ups to help prevent heart disease, stroke, diabetes and kidney disease.
3. The vascular system is made up of all of the blood vessels in the body. The arteries and veins, powered by the heart, carry blood throughout the body, delivering oxygen and nutrients that power muscles and organs.
4. Vascular diseases are linked by having shared causes and complications, namely the build-up of fatty deposits (called atheroma or plaque) that block or weaken blood vessels.
5. These deposits cause serious vascular diseases around the body, including coronary heart disease (CHD), stroke, chronic kidney disease (CKD), and diabetes. 6. Vascular diseases are also linked because they share similar risk factors. For example, smoking, physical inactivity, high blood pressure and raised cholesterol can all lead to a build-up of fatty deposits in the blood vessels.
7. Vascular diseases often occur together and having one condition greatly increases chances of having one of the others. For example, adults with diabetes have heart disease rates of up to four times higher than adults without diabetes, and two of the main causes of kidney disease are high blood pressure and diabetes.
http://www.dh.gov.uk
Siemens Introduces New Dual Energy Applications For The SOMATOM Definition Dual Source
April 1, 2008
Siemens announced the market clearance of four new applications for the SOMATOM Definition Dual Source at ECR 2008 in Vienna. The new applications have been designed to simplify the diagnosis of diseases in the heart, brain, lungs and extremity joints.
With a dual X-ray tube and dual-detector design, the SOMATOM Definition DS provides images at twice the temporal resolution, twice the speed and twice the power of single-source systems. The two X-ray tubes can be operated simultaneously at different voltage levels (dual energy or DE) in a single scan, generating two data records with different patient information to display tissue and fluids, facilitating the distinction of vessels, bones and soft tissue. It acquires images of outstanding quality and detail, even imaging hearts with irregular beats at only half the dose of previous Siemens systems.
One of the new dual energy applications for the SOMATOM Definition DS is syngo® DE Heart PBV (Perfusion Blood Volume), which provides colour-marking of non-perfused parts of the myocardium during cardiology examinations. This application enables an isolated display of the heart, for example, without thorax structures. For the first time, DECT can detect narrowed blood vessels as well as the location and extent of the resulting reduced perfusion in a single scan.
With syngo DE Gout, CT can now also be used for gout detection. The new dual energy application assists the physician in clearly identifying and monitoring uric acid crystals for precise diagnosis and efficient treatment planning.
syngo DE Lung Vessels provides a whole series of applications to assist the physician in CT examinations of patients with suspected pulmonary embolism. The new applications enable the detection of non-perfused blood vessels and tissue of the lungs through colour-marking. The “lung isolation” application isolates the entire organ to allow the assessment of the perfusion situation without obstructing other organs.
syngo DE Brain Haemorrhage assists in the distinction between new and old haemorrhages in the event of cerebral bleeding without the need for two separate scans. The two energy levels of the X-ray tubes are used to fade out the contrast medium (CM), eliminating the need for a non-contrast medium enhanced examination, reducing dose to the patient.
“The SOMATOM Definition DS already offers enhanced resolution, speed and power. These new diagnostic applications add a further dimension to assist with disease prevention and treatment,” said Russell Lodge, CT Product Manager at Siemens. “Contrast in the image is not merely limited to X-ray attenuation differences, but includes elements of functional and tissue characterisation. This additional information will help to improve diagnostic outcomes and simplify workflows.”
The four new dual energy applications presented by Siemens at the ECR 2008 supplement the six existing CT applications with dual energy features:
- syngo DE Direct Angio - distinguishes bone and vessel structures, particularly if the vessels are located directly next to the bone.
- syngo DE Lung PBV - for perfusion assessment of the lung tissue.
- syngo DE Musculoskeletal - displays ligaments and tendons.
- syngo DE Calculi Characterisation - automatically distinguishes the biochemical composition of kidney stones.
- syngo DE Hardplaque - displays calcification in the body and determines vessel status.
- syngo DE Virtual Unenhanced - for subtraction of contrast medium in abdominal scans.
Siemens Healthcare is one of the world’s largest suppliers to the healthcare industry. The company is a renowned medical solutions provider with core competence and innovative strength in diagnostic and therapeutic technologies as well as in knowledge engineering, including information technology and system integration. With its laboratory diagnostics acquisitions, Siemens Healthcare is the first fully integrated diagnostics company, bringing together imaging and lab diagnostics, therapy and healthcare information technology solutions, supplemented by consulting and support services. Siemens Healthcare delivers solutions across the entire continuum of care - from prevention and early detection, to diagnosis, therapy and care. The company employs more than 49,000 people worldwide and operates in 130 countries. In the fiscal year 2007 (Sept. 30), Siemens Healthcare reported sales of €9.85 billion, orders of €10.27 billion and group profit of €1.32 billion.
Siemens Healthcare
CytRx To Present Stroke Recovery Data At The Sixth International Workshop On The Molecular Biology Of Stress Responses
March 28, 2008
CytRx Corporation (Nasdaq: CYTR), a biopharmaceutical company engaged in the development and commercialization of human therapeutics, announced that Shi Chung Ng, Ph.D., CytRx’s Senior Vice President of Research and Development, will present previously reported positive results of several animal stroke studies with the Company’s lead molecular chaperone amplification drug candidate arimoclomol at the Sixth International Workshop on The Molecular Biology of Stress Responses being held at the Chulabhorn Research Institute in Bangkok, Thailand.
In his presentation, Dr. Ng will discuss study data indicating that while motor skills declined dramatically in study rats immediately after stroke was induced, those treated orally with arimoclomol recovered dramatically faster and more completely than untreated animals, regardless of whether arimoclomol treatment was initiated six, 12, 24 or even 48 hours after stroke was induced. Animals treated 48 hours post-stroke-inducement were approximately half-way to complete recovery within seven days after stroke, while motor skills of untreated animals had not improved.
“We believe that stroke recovery with arimoclomol represents a new paradigm in stroke pharmaceutical intervention that we refer to as ‘neurorestoration,’” said Dr. Ng. “Most of the previous-generation stroke drug candidates that have been tested in recent years were designed to prevent brain cells from dying in the acute stage of ischemic stroke, either by re-establishing the flow of blood (fibrinolytics or clot busters) or by protecting the cells from the absence of oxygen (neuroprotectants). The results of our studies presented at this meeting suggest that arimoclomol improves recovery from stroke not by decreasing the number of brain cells that die, but by repairing the brain cells that survived but that were otherwise too injured to function normally. This may explain why arimoclomol demonstrated statistically significant improvement in recovery even when the drug was administered well after the event. We are pleased to share the results of our study at this important workshop that attracts scientific thought-leaders from around the world.”
“On average, every 40 seconds someone in the U.S. has a stroke, and stroke is the number one cause of long-term disability among Americans, according to the American Heart Association,” added CytRx’s Chief Scientific Officer Jack Barber, Ph.D. “The results from these rat studies with arimoclomol in stroke recovery are sufficiently compelling that we are working toward entering a Phase II clinical trial in stroke recovery in the second half of this year, subject to U.S. Food and Drug Administration (FDA) clearance.”
About CytRx Corporation
CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The Company owns three clinical-stage compounds based on its small molecule “molecular chaperone amplification” technology. In September 2007, CytRx announced that arimoclomol was shown to be safe and well-tolerated at all three doses tested in its Phase IIa clinical trial in patients with ALS. The Company’s Phase IIb clinical trial with arimoclomol for ALS was placed on clinical hold in January 2008, and the Company has announced its intention to work diligently with the FDA to reach resolution. The FDA has granted Fast Track designation and Orphan Drug status to arimoclomol for the treatment of ALS, which has also been granted orphan medicinal product status for the treatment of ALS from the European Medicines Agency. The Company has announced plans to commence a Phase II clinical trial for arimoclomol in stroke recovery in the second half of 2008, subject to FDA clearance. The Company has also announced plans to commence a Phase II clinical trial with its next drug candidate, iroxanadine, for diabetic foot ulcers in the second half of 2008, subject to FDA clearance. CytRx has recently opened a research and development facility in San Diego. For more information on the Company, visit http://www.cytrx.com.
Forward-Looking Statements
This press release may contain forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks or uncertainties related to the outcome or results of any future pre-clinical or clinical testing of arimoclomol for stroke recovery, uncertainties related to the impact of the FDA’s clinical hold on our clinical program for arimoclomol for the treatment of amyotrophic lateral sclerosis on the timing and ability to initiate the planned Phase II clinical trial for stroke recovery, the risk that any requirements imposed on our planned clinical trial design for stroke recovery by the FDA as a result of the concerns expressed in their clinical hold of our ALS program might adversely affect our ability to demonstrate that arimoclomol is efficacious in treating stroke patients or cause us to cancel the trial, the potential need to conduct additional toxicology or human studies which could result in substantial additional expenses and delay the resumption of the clinical trial, as well as other risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
CytRx Corporation
Hispanics With Artery Buildup Have Greater Risk Of Vascular Events Than Blacks, Whites, Study Finds
March 21, 2008
Hispanics who have just a small amount of plaque buildup in a particular artery in the neck are up to four times more likely than others with clear arteries to have or die from a stroke, heart attack or other vascular event, according to a study published in the current issue of Neurology, HealthDay/U.S. News & World Report reports (HealthDay/US. News & World Report, 3/19). Blacks, whites and others with moderate buildup did not have the same risks (Norton, Reuters Health, 3/19).
The study involved nearly 2,200 adults who participated in the multiethnic Northern Manhattan Study in New York City (HealthDay/U.S. News & World Report, 3/19). More than half of the participants were Hispanic (Reuters Health, 3/19). Through the use of ultrasound scans, study author Tatjana Rundek of the Miller School of Medicine at the University of Miami and colleagues found that 58% of the participants had plaque buildup in their carotid artery, which supplies blood to the brain. Twenty-five percent had maximum buildup (HealthDay/U.S. News & World Report, 3/19). Hispanics were less likely to have plaque buildup than whites or blacks, but when they did have buildup, it appeared to be more severe than what was found in others, the study indicates (Reuters Health, 3/19).
Researchers followed up with the participants after seven years and found that 121 had or died of ischemic stroke, 118 had suffered or died of heart attack and 166 had died of other vascular events (HealthDay/U.S. News & World Report, 3/19). In addition, Hispanics with a maximum plaque buildup had a greater risk of having a “vascular event” than those with less or no plaque buildup, according to the study.
Researchers did not find an explanation for Hispanics’ increased risk of vascular events. According to Rundek, plaque could progress more quickly in Hispanics or their plaque buildup could be more susceptible to rupture (Reuters Health, 3/19).
“More research is needed … to determine why Hispanics with even small amounts of carotid plaque are particularly susceptible to vascular events,” Rundek said, adding, “These results are important for developing stroke and vascular prevention programs for all, but also for certain ethnic groups such as Hispanics, who represent the fastest-growing minority population in the U.S.” (HealthDay/U.S. News & World Report, 3/19).
An abstract of the study is available online.
Reprinted with kind permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation© 2007 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
Magnesium May Lower Risk for Some Strokes in Male Smokers
March 20, 2008
March 11 — Increased consumption of magnesium-rich foods such as whole grains may reduce male smokers’ risk of cerebral infarction, which occurs when blood flow to the brain is blocked, a new Swedish study suggests.
Researchers at the Karolinska Institute in Stockholm analyzed the diets and other health/lifestyle habits and characteristics of 26,556 Finnish men, aged 50 to 69, who smoked but had never had a stroke. During an average of 13.6 years of follow-up, 2,702 of the men had cerebral infarctions, 383 had intracerebral hemorrhages , 196 had subarachnoid hemorrhages , and 84 had unspecified types of strokes.
After they adjusted for age and cardiovascular risk factors , the researchers concluded that men who consumed the most magnesium had a 15 percent lower risk for cerebral infarction than those who consumed the least amount of magnesium . The association was stronger in men younger than 60.
There was no association between magnesium consumption and risk for intracerebral or subarachnoid hemorrhage, said the researchers, who added that calcium, potassium and sodium intake weren’t associated with risk for any type of stroke.
The findings were published in the March 10 issue of the Archives of Internal Medicine.
"An inverse association between magnesium intake and cerebral infarction is biologically plausible," the study authors wrote. Magnesium lowers blood pressure and may also affect cholesterol concentrations and the body’s use of insulin to turn glucose into energy, both of which would affect the risk for cerebral infarction, but not hemorrhage.
"Whether magnesium supplementation lowers the risk of cerebral infarction needs to be assessed in large, long-term randomized trials," the study authors added.
Recent studies have suggested that changes in diet may help reduce stroke risk, according to background information in the study. High blood pressure is a risk factor for stroke, which means that dietary changes that lower blood pressure may reduce stroke risk.
SOURCE: JAMA/Archives journals, news release, March 10, 2008
Mechanisms Suggest New Way To Treat Heart Disease Among Diabetics
March 14, 2008
Researchers have discovered how diabetes, by driving inflammation and slowing blood flow, dramatically accelerates atherosclerosis, according to research to be published in the March 14 edition of the journal Circulation Research.
Experts once believed that atherosclerosis, or hardening of the arteries, developed when too much cholesterol clogged arteries with fatty deposits called plaques. When blood vessels became completely blocked, heart attacks and strokes occurred. Today most agree that the reaction of the body’s immune system to fatty build-up, more than the build-up itself, creates heart attack risk. Immune cells traveling with the blood mistake fatty deposits for intruders, akin to bacteria, home in on them, and attack. This causes inflammation that makes plaques more likely to swell, rupture and cut off blood flow.
Making matters worse, nearly 21 million Americans have diabetes, a disease where patients’ cells cannot efficiently take in dietary sugar, causing it to build up in the blood. In part because diabetes increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke.
Past work has shown that high blood sugar has two effects on cells lining blood vessels as part of atheroslerosis. First, it increases the production of free radicals, highly reactive molecules that tear about sensitive cell components like DNA, causing premature cell death (apoptosis). This process also reduces the availability of nitric oxide (NO), which would otherwise enable blood vessels to relax and blood flow to increase. In contrast to diabetes, exercise and good diet bring about faster blood flow through blood vessels. The force created by fast, steady blood flow as it drags along blood vessel walls has been shown by recent studies to protect arteries from atherosclerosis. Physical force has emerged recently as a key player in bodily function, capable of kicking off biochemical processes (e.g. weightlifting thickens bone).
“Inflammation is blood vessels is one of the main drivers of atherosclerosis, and diabetes makes it much worse,” said Jun-ichi Abe, M.D., Ph.D., associate professor with the Aab Cardiovascular Research Center at the University of Rochester Medical Center, and a study author. “Our study argues that a pathway surrounding a key signaling enzyme both protects the heart in normal cases, and is sabotaged by the chemicals produced in diabetes. We believe we have found a new therapeutic target for the treatment of diabetes-related damage to blood vessels.”
How Diabetes Does It
In people without diabetes, fast blood flow triggers an enzyme called extracellular signal-regulated kinase 5 (ERK-5). ERK5 in turn signals endothelial nitric oxide synthase (eNOS) to produce more nitric oxide and dilate blood vessels. It also activates Kruppel-like factor 2 (KLF2) and peroxisome proliferator-activated receptor-g (PPARg), both of which block the ability of pro-inflammatory immune cells to home in on and adhere to diseased portions of blood vessels.
Past studies had shown diabetes to worsen atherosclerosis, but its exact link to related inflammation had remained unclear. The current results provides the first mechanistic description of how diabetes takes away the ability of fast blood flow force to protect blood vessels, arguing that it does so by interfering with ERK5 and its signaling partners.
Abe’s team showed that molecules called advanced glycation end products (AGEs), produced in greater levels by patients with diabetes, interfere with ERK5 cardioprotection. Glycation reactions cause the release of oxidizing side products like hydrogen peroxide (H202) that drive free radical production, inflammation and cell damage in many diseases.
Researchers found that AGEs and H202 sabotage ERK5 by encouraging the attachment to it of a small ubiquitin-related modifier (SUMO), a protein tag used by cells to fine-tune their control over proteins. In normal function, a cell may extend a protein’s lifespan, or send it from one part of the cell to another, by attaching a SUMO tag. In the current study, researchers found that AGEs and H202 induced ERK5-SUMOylation as part of disease. In addition, the team found that ERK5-SUMOylation was increased in the aortas of diabetic mice.
Along with Abe, Chang-Hoon Woo, Tetsuro Shishido and Carolyn McClain contributed to the work within the Aab Cardiovascular Research Center. Jae Hyang Lim and Jian-Dong Li within the Department of Microbiology & Immunology at the Medical Center contributed expertise, along with Jay Yang, professor of Anesthesiology at Columbia University. This work is supported by grants from the America Heart Association and the National Institutes of Health.
“Our experiments found that taking away the “SUMO tag” from ERK protects blood vessels against diabetes,” Abe said. “We believe that the SUMOylation of ERK turns off ‘good’ genes that are important in countering atherosclerosis. In the next phase, we will be looking for drug candidates that can turn on ERK5 as diabetes attempts to shut it down.”
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Source: Greg Williams
University of Rochester Medical Center
New Educational Effort Launched On Genetic Testing For Dosing A Common Blood Thinner
March 13, 2008
A new educational effort focused on improving the safety and reducing the complications of a life-saving heart drug was launched by the American Medical Association (AMA) and the Critical Path Institute (C-Path), as part of an ongoing program to support personalized medicine. The groups collaborated on a new educational brochure to inform health care practitioners about how patients’ genetics influence their response to warfarin, and the genetic tests available to determine the best initial dose of the drug. Warfarin is commonly prescribed to patients to prevent blood clots, heart attacks and strokes and is also known under the brand names of Coumadin, Jantoven, Marevan and Waran.
The FDA estimates that two million patients in the U.S. start taking warfarin every year and it has been prescribed to patients for more than 50 years. Warfarin can provide enormous benefits, but the safe and effective dose varies greatly among patients. It is the second most common drug, after insulin, implicated in emergency room visits for adverse drug events, especially bleeding complications.
“Warfarin’s effectiveness is widely known within the medical community, but it is underutilized because of concerns about the risk of bleeding complications,” said AMA Board Member and cardiovascular disease specialist James Rohack, MD.
In August, the FDA changed the official labeling of warfarin to inform practitioners that genetic testing may help providers improve the initial dosing for individual patients.
“Studies show that genetic factors explain why 40 percent of patients taking warfarin are more sensitive to the drug and require a smaller dose,” said Dr. Rohack. “Genetic testing can identify patients at high risk for bleeding complications when warfarin is started, and allow the physician to use smaller doses to reduce the initial bleeding risk.”
“The brochure outlines the science behind genetic testing for warfarin dosing so physicians can incorporate this form of personalized health care into their practices,” said Raymond Woosley, MD, PhD, President and CEO, C-Path. “The FDA is to be commended for its work to update the label and help inform the medical community of this modern scientific advancement that can improve a commonly prescribed medicine.”
American Medical Association
Binge Drinking Brits Risk Brain Damage, UK
March 12, 2008
The Stroke Association is warning the public of the dangers of binge drinking and how it can increase your risk of brain damage from a stroke.
The warning comes at the start of Brain Awareness Week 2008. Binge drinking can raise blood pressure to dangerously high levels and is a major risk factor for stroke. A stroke is a brain attack; it happens when the blood supply is cut to the brain causing brain cells to die and results in brain damage. Stroke is the UK’s third biggest killer and if it doesn’t kill it could leave you paralyzed, unable to talk, walk and/or incontinent.
People who binge drink (consume six or more units at a single sitting) are twice as likely to have a stroke than non-drinkers. Yet, worryingly an estimated 60% of people are not aware that stroke can be a consequence of binge drinking. Current government statistics indicate that 18% of men and 8% of women drank more than 8 units and 6 units respectively, on at least one day in the previous week.
Despite this only 25% of people questioned in a survey said that they would reduce their alcohol intake to help reduce their risk of stroke. The number of people, who already do so, was only slightly higher at 31%.
These figures are of some concern, especially given that heavy intermittent drinking is a feature of many peoples social lives in the UK and young people are more inclined to consume more than twice the recommended sensible drinking limit. Joe Korner, Director of Communications at The Stroke Association said:
“Stroke can be a devastating condition and can affect anyone, of any age at any time. By binge drinking you are increasing your risk of stroke and leaving yourself vulnerable to serious consequences such as long term disability or even death. Therefore The Stroke Association is urging the public, not just for Brain Awareness Week, but for the whole year round to exercise control over the amount of alcohol they are consuming.”
Notes
1. The Stroke Association conducted a survey on binge drinking across the UK. 1909 people were surveyed between 19-22 November 2004. Markettiers4DC carried out the survey on behalf of The Stroke Association.
2. The Stroke Association is the only UK wide charity solely concerned with combating stroke in people of all ages. The charity funds research into prevention, treatment, better methods of rehabilitation and helps stroke patients and their families directly through its community services, welfare grants, publications and leaflets. The Stroke Association also campaigns, educates and informs to increase knowledge of stroke at all levels of society acting as a voice for everyone affected by stroke.
3. A stroke is a brain attack which causes brain damage. A stroke can be diagnosed using FAST - Facial weakness, Arm weakness, Speech problems, Test all three. If any of these symptoms are present call an ambulance straight away.
4. The Stroke Helpline provides information on stroke to the general public and is open between 9am and 5pm Monday to Friday on 0845 3033 100
The Stroke Association
Discovery Opens The Way To Clinical Development Of The First Safe Clot Busting Agent For Treating Heart Attacks And Strokes
March 11, 2008
A team of researchers at Oregon Health & Science University and Washington University in St. Louis have described for the first time the mechanism that gives a mutant enzyme molecule that they have engineered - and patented - the potential to become a breakthrough drug for treating heart attacks and strokes.
The team described how their genetically modified enzyme, called WE-thrombin, functions as a potent clot busting agent while retaining little of the power that thrombin, its non-engineered parent, has to cause the opposite result, a cascade of clot building. They did so in a paper published recently in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a peer-reviewed journal of the American Heart Association. An editorial commentary in ATVB hailed this breakthrough as “a significant advance in understanding the functions and antithrombotic potential of (WE thrombin) in particular, and the approach of using engineered human proteins more broadly…”
“The successful development of WE-thrombin would be a major medical breakthrough in antithrombotic therapy, ultimately saving thousands of lives worldwide each year,” said the lead investigator András Gruber, M.D., Ph.D., associate professor of medicine in the division of hematology and medical oncology, OHSU School of Medicine.
Thrombin is an enzyme that, paradoxically, has the capacity both to promote and prevent blood clotting. Balancing the two depends on a highly complex system of positive and negative feedback loops. Normal blood clotting is vital to minimize bleeding in the event of an injury. Excessive clotting can lead to thrombosis, the blockage of a blood vessel.
Heart attacks and strokes - most often the result of blood clots - remain two of the three leading causes of death and severe disability in the United States. The toll from these diseases persists at high levels in part because the drugs now relied on to stop or break up clots - such as heparin or TPA, tissue plasminogen activator - pose the risk of triggering hard-to-control systemic bleeding. Also, they can’t be injected outside of a clinical setting in patients that present with symptoms of stroke or heart attack and, even then, only after time consuming preliminary diagnostic tests and scans. Every minute that treatment is delayed after the onset of a stroke or heart attack reduces the odds of survival or recovery.
The researchers contemplate that, if it is approved for use in humans, WE thrombin - which the research team has demonstrated is effective and safe in large primates - could safely be injected by paramedics or others, whenever someone displays the first symptoms and signs of a stroke or heart attack without fear of causing harm if the symptoms prove to be a false alarm.
Aronora LLC, a startup biotechnology company, has been formed by Gruber along with the primary co-investigators and others, to seek financial support for preclinical and early clinical development of WE-thrombin as a safe alternative to existing antithrombotic drugs. The market for such drugs is estimated to exceed $20 billion per year worldwide. The patents on WE-thrombin are currently co-owned by the investigators’ parent institutions, OHSU, Emory University and Washington University.
“WE-thrombin is the most potent antithrombotic agent that ever has been described,” said Gruber. “And that’s because of its specificity. It effectively utilizes a natural “drug delivery system” of circulating blood platelets and white blood cells that accumulate in the clot formation process to deliver its punch directly to a blood clot. The process parallels that of targeted drug delivery. It’s effective inside a blood vessel, but not at all effective outside the blood stream, which is exactly what you want from an antithrombotic agent.”
“What we’ve done recently,” added coinvestigator Owen J.T. McCarty, Ph.D., “is located the exact point where the catalytic reaction takes place in vivo that makes this molecule work as a superior antithrombotic agent.” McCarty, an expert in platelet biology, is assistant professor of biomedical engineering in the department of cell and developmental biology, OHSU School of Medicine.
Blood platelets are small cells that sense an injury and rush to form a clot to reduce bleeding. They do so by binding thrombin, which cuts fibrinogen into strands of fibrin to form the “glue” of a clot. The process becomes self sustaining, or autocatalytic, which means that the glue is produced and reproduced in a rapid chain reaction. Thrombin subsequently counterbalances the process by activating protein C inside the blood vessel, which shuts down the autocatalytic reaction in the blood stream.
WE-thrombin, the mutant form of thrombin, lacks the ability to create the glue but still can produce activated protein C (APC) inside the blood vessels, which makes it a unique, locally acting anticoagulant. The molecule enhances this ability, the research team discovered, by attaching itself to a receptor, or sticking point, called glycoprotein Ib (GPIb), located on the surface of platelets. In doing so, WE-thrombin shoulders aside - and thus inhibits - the protein (the von Willebrand factor) that promotes coagulation, which now has to compete for the same receptor on the platelets.
Because of WE-thrombin’s specificity and potency, the dosage required to be effective in humans, Gruber said, is expected to be less than 0.5 milligrams, and possibly less than 0.1 milligrams, or 200- to 1,000-fold less than the dosage levels of TPA commonly being administered now in heart attack and stroke.
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The current findings were built, in part, on years of work by co-investigator Enrico Di Cera, M.D., Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics and professor of medicine at Washington University, on enzyme complexes relevant to the clotting process and protein engineering. Several members of the collaborative team of investigators that also include Stephen R. Hanson, Ph.D., professor of biomedical engineering at OHSU (who formerly was at Emory University), are among the world’s leaders in thrombin, protein C and thrombosis research. Co-authors of the study, “Thrombin Mutant W215A/E217A Acts as a Platelet GPIb Antagonist,” published in Arteriosclerosis, Thrombosis, and Vascular Biology [2008 Feb: 28 (2): 329-34], also included Michelle A. Berny, Tara C.White, and Erik I. Tucker, all graduate students in biomedical engineering, OHSU School of Medicine; and Leslie A. Bush-Pelc, senior research assistant at Washington University. Berny and White are Achievement Rewards for College Scientists Foundation Scholars.
Funding and other assistance has been provided by the OHSU Springboard Program for new ventures and research grants from the National Institutes of Health and the American Heart Association.
Potential conflicts of interest involving OHSU investigators and start-up companies are reviewed by the OSHU Conflict of Interest in Research Committee and the OHSU Integrity Program Oversight Council.
About OHSU
Oregon Health & Science University is the state’s only health and research university, and its only academic health center. It is Portland’s largest employer and the fourth largest in Oregon (excluding government), with more than 12,400 employees. As a leader in research, OHSU earned $307 million in research funding in fiscal year 2007. OHSU serves as a catalyst for the region’s bioscience industry and is an incubator of discovery, averaging one new breakthrough or innovation every 2.7 days, with more than 4,100 research projects currently under way. OHSU disclosed 132 inventions in 2007 alone, and OHSU research has resulted in 33 startup companies since 2000, most of which are based in Oregon.
Source: Harry Lenhart
Oregon Health & Science University
