Gore Provides Update On Patent Foramen Ovale (PFO) Stroke Study

W. L. Gore & Associates (Gore) provided an update on the Gore REDUCE Clinical Study*, a prospective, randomized, multi-center, multi-national trial designed to demonstrate safety and effectiveness of the GORE HELEX Septal Occluder for Patent Foramen Ovale (PFO) closure in patients with history of cryptogenic stroke or imaging-confirmed Transient Ischemic Attack (TIA). The unique study, which includes up to fifty investigational sites in the U.S., Denmark, Finland, Norway and Sweden, is on track to meet its estimated completion in 2015.

“In light of the recent press release regarding the preliminary results of CLOSURE I, we felt it important to re-emphasize our confidence in the design and expected outcome of the Gore REDUCE Clinical Study,” said Stuart Broyles, PhD, Associate with the Gore Medical Division Stroke Business. “Due to our European experience regarding the clinical performance of the GORE HELEX Septal Occluder and our unique study design, we remain very confident that the Gore REDUCE Clinical Study will ultimately achieve its intended objective. We are committed to the completion of this study and the pursuit of an FDA indication for PFO closure and the prevention of recurrent stroke.”

According to Scott Kasner, MD, Professor of Neurology and Director of the Comprehensive Stroke Center at the University of Pennsylvania Medical Center, and U.S. Neurology Principal Investigator, “The design of the Gore REDUCE Clinical Study is unique from the other PFO stroke trials in several respects. First, Magnetic Resonance Imaging (MRI) of the brain will be performed on all patients at baseline and at two years. This feature offers an additional imaging endpoint for making comparisons between the treatment arms. Second, it focuses on secondary prevention of stroke rather than TIA, which improves the reliability of the study outcomes and measurably impacts the public health. Finally, this is a multinational study, which enhances its global applicability. These efforts will likely help resolve the open debate about whether PFO closure is a viable option for treating cryptogenic stroke / TIA patients as compared to medical treatment alone, as it is used today.”

The Gore REDUCE Clinical Study has several unique features: participation of Nordic investigational sites, the use of imaging-confirmed stroke / TIA for assessing its primary endpoint, a 2:1 device to medical management randomization strategy, a standardization of medical therapies across treatment arms, and the use of the GORE HELEX Septal Occluder. Recruitment in the Nordic countries, where patients may be more willing to be randomized, is projected to help drive study enrollment. Additionally, Gore is in the process of recruiting sites in the United Kingdom to participate in the Gore REDUCE Clinical Study. MRI will be used to evaluate all patients in the trial to more accurately confirm the presence of stroke and TIA. Additionally, the standardization of medical therapies across treatment arms will further aid the interpretation of the final results in assessing the potential benefit of device closure for the prevention of recurrent stroke. The GORE HELEX Septal Occluder was approved by the U.S. Food and Drug Administration (FDA) in 2007 for treatment of Atrial Septal Defect (ASD), a congenital heart defect. The GORE HELEX Septal Occluder is the first device of its kind to use ePTFE, a biocompatible material that allows progressive tissue ingrowth, to help seal the defect.

*REDUCE: Gore® HELEX Septal Occluder plus Anti-platelet medical Management for Reduction of Recurrent Stroke or Imaging – Confirmed TIA in Patients with PFO.


W. L. Gore & Associates

FDA Approves GlaxoSmithKline’s VOTRIENT(TM) For Advanced Renal Cell Cancer

GlaxoSmithKline (NYSE: GSK) announced that the U.S. Food and Drug Administration (FDA) has approved VOTRIENT(TM) (pazopanib) to treat patients with advanced renal cell carcinoma (RCC), a form of kidney cancer. Approximately 57,700 people in the U.S. will be diagnosed with kidney cancer this year, and 13,000 people will die from this disease.

“RCC is the most common malignancy of the kidney and is highly resistant to chemotherapy,” said Paolo Paoletti, MD, Senior Vice President, GlaxoSmithKline Oncology R&D Unit. “While treatment has improved in the past few years with the introduction of targeted therapies, advanced RCC remains a challenging disease. VOTRIENT will join existing targeted therapies to provide physicians with a new oral treatment option to their patients with advanced renal cell cancer.”

VOTRIENT, a once-daily, oral medication, is an angiogenesis inhibitor which may help prevent the growth of new blood vessels, thereby blocking the growth of kidney cancer tumors that need blood vessels to survive.

The approval of VOTRIENT was supported by a unanimous decision by the FDA’s Oncology Drugs Advisory Committee (ODAC) that the benefit-to-risk profile for VOTRIENT is acceptable for patients with advanced kidney cancer. The ODAC reviewed data from a Phase III clinical trial showing that VOTRIENT reduced the risk of tumor progression or death by 54 percent compared to placebo, regardless of prior treatment.

In this Phase III trial, the overall median PFS was 9.2 months with pazopanib and 4.2 months with placebo. Treatment-naive patients who received VOTRIENT experienced 11.1 months of median progression-free survival (PFS) versus 2.8 months with placebo. Additionally, patients who had previously received cytokine-based treatment achieved 7.4 months of median PFS with VOTRIENT versus 4.2 months with placebo.

The most common adverse events occurring in greater than or equal to 20% of subjects treated with VOTRIENT included diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. Grade 3/4 adverse events among these toxicities that differed by greater than or equal to 2% included abnormal liver function, hypertension, diarrhea, asthenia, and abdominal pain. Laboratory abnormalities occurring in >10% of patients and more commonly (greater than or equal to 5%) in the pazopanib arm included increased transaminases, hyperglycemia, leukopenia, hyperbilirubinemia, neutropenia, hypophosphatemia, thrombocytopenia, lymphocytopenia, hyponatremia, hypomagnesemia, and hypoglycemia. Drug-related deaths were observed in 1.4% of 290 patients and included hepatic failure (n=2), stroke (n=1), and perforation (n=1). Hepatic dysfunction is included as a boxed warning in the product label. Other Warnings and Precautions in the label relate to QT prolongation and torsade de pointes, hemorrhagic events, arterial thrombotic events, gastrointestinal perforation and fistula, hypertension, impaired wound healing, hypothyroidism, proteinuria, and pregnancy.

About GSK Oncology

GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s revolutionary ‘bench to bedside’ approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes collaborations with more than 160 cancer centers. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK’s operations are described under ‘Risk Factors’ in the ‘Business Review’ in the company’s Annual Report on Form 20-F for 2008.

Source: GlaxoSmithKline

View drug information on Votrient.

Organ Donation Criteria Can Be Expanded, Studies Suggest

What makes a donated kidney or pancreas “acceptable” for transplant? Results from two pilot studies suggest that it may
be possible to expand the current acceptance criteria for deceased donors, which could significantly increase the number of
organs available for transplant each year.

“We are encouraged by our success using organs from deceased donors that would ordinarily have been discarded,” said Robert
Stratta, M.D., director of Transplantation Services at Wake Forest University Baptist Medical Center, in an interview. “Even
organs donated after cardiac death can be suitable in some cases, which has been taboo in the past.”

In 2002, the United Network for Organ Sharing (UNOS) expanded the criteria for kidney donors so that higher risk donor
organs, once considered unsuitable, could now be transplanted safely. The number of kidney transplants performed at Wake
Forest Baptist has doubled by using expanded criteria donors (ECDs).

In the current studies, Stratta and colleagues went a step further and looked at success rates using organs at the outer
limits of acceptance criteria, which Stratta refers to as organs from “extreme” donors. The researchers found that patient
and organ survival rates in transplants involving extreme donors were similar to success rates with conventional donors.
Stratta reported the results last week at the American Transplant Congress 2005 meeting in Seattle, Wash., and earlier in May
at the 10th Annual Congress of the International Pancreas and Islet Transplant Association in Geneva, Switzerland.

“The shortage of donated organs is a national crisis, with people on the waiting list dying every day,” said Stratta. “This
mandates an ongoing reappraisal of the limits of donor organ acceptability.”

Both studies were retrospective – looking back at success rates of patients who had transplants performed. One study involved
patients who had a simultaneous kidney-pancreas transplant, and the other involved patients receiving a kidney transplant

Ideal pancreas donors are between the ages of 10 and 40 years, weigh between 60 and 180 pounds, and die in the hospital from
a head injury. Because of the strict criteria for pancreas donors, the pancreas is recovered in only 20 to 25 percent of
organ donors nationally.

Stratta’s study defined extreme kidney-pancreas donors as those who were either older than 50 or younger than 8 years, or who
died after their heart stopped. People with cardiac death are often considered inappropriate for pancreas donation because
their organs may become damaged from being oxygen-deprived.

With a mean followup of 17 months, the average organ survival rate in patients who received a pancreas from an extreme donor
was 89 percent. The organ survival rate in the conventional group, which had a mean followup of 22 months, was 77 percent.
Patient survival rates were 100 percent in the extreme donor group and 93.5 percent in the conventional group. There were no
significant differences in length of hospital stay, incidence of acute rejection, infection or surgery complications. The
study involved 31 transplants from conventional donors and nine transplants from extreme kidney-pancreas donors.

“Our results suggest that the pancreas donor criteria can be liberalized to include selected female donors who are over 50
years of age, pediatric donors, and donation after cardiac death without incurring any adverse short-term outcomes,” said
Stratta. “These short-term results are significant because they are comparable to the already excellent results achieved from
standard or more conventional pancreas donors.”

The second study involved patients who received kidneys from extreme ECDs between October 2001 and November 2004. Extreme
ECDs were defined as deceased donors who were at the outer limits of acceptability including being older than 70 years,
having high levels of a protein called creatinine, which is used to determine kidney function, dying from cardiac arrest
prior to organ donation, or prolonged storage time for the organ.

The researchers compared 32 kidney transplants involving conventional ECDs with 42 from extreme ECDs. After a mean followup
of 18 months, kidney survival was 83 percent in the extreme ECD group and 84 percent in the conventional ECD group. Patients
in the extreme ECD group had an average survival of 95 percent, compared to 86 percent in the conventional ECD group. Renal
function was comparable in both groups.

“The limits of donor acceptability continue to evolve as excellent short-term outcomes can be achieved in kidney transplants
from extreme donors. More importantly, patients are waiting less time to receive a life-saving kidney transplant and become
dialysis-free,” said Stratta.

Wake Forest University Baptist Medical Center
Medical Center Blvd.
Winston-Salem, NC 27157-1015
United States

Veterinary Experts To Gather In Washington, D.C., For AVMA Annual Convention

The nation’s veterinarians will be meeting this summer in Washington, D.C., for the American Veterinary Medical Association’s 144th Annual Convention, and you are invited to attend!

The convention, held July 14-18 at the Washington Convention Center, will feature some of the nation’s leading veterinary experts discussing a wide variety of topics on veterinary medicine and public health, including avian influenza, bioterrorism, pet nutrition, alternative medicine, and much more. In all, more than 1,000 topics will be discussed by 600 world-renowned experts over the 5-day convention.

In addition, the convention will begin with a presentation by keynote speaker Julie Gerberding, MD, MPH, director of the Centers for Disease Control and Prevention, who will discuss CDC’s focus on diseases spread by animals and the increased importance of veterinarians in public health.

The AVMA, founded in 1863, is one of the oldest and largest veterinary medical organizations in the world, with more than 75,000 member veterinarians engaged in a wide variety of professional activities. AVMA members are dedicated to advancing the science and art of veterinary medicine, including its relationship to public health and agriculture. Visit the AVMA Web site at www.avma to learn more about veterinary medicine and animal care and to access up-to-date information on the association’s issues, policies and activities.

Lower Stroke Risk In Women Who Walk Regularly

Women who walked two or more hours a week or who usually walked at a brisk pace (3 miles per hour or faster) had a significantly lower risk of stroke than women who didn’t walk, according to a large, long-term study reported in Stroke: Journal of the American Heart Association.

The risks were lower for total stroke, clot-related (ischemic) stroke and bleeding (hemorrhagic) stroke, researchers said.

Compared to women who didn’t walk:
Women who usually walked at a brisk pace had a 37 percent lower risk of any type of stroke and those who walked two or more hours a week had a 30 percent lower risk of any type of stroke.

Women who typically walked at a brisk pace had a 68 percent lower risk of hemorrhagic stroke and those who walked two or more hours a week had a 57 percent lower risk of hemorrhagic stroke.

Women who usually walked at a brisk pace had a 25 percent lower risk of ischemic stroke and those who usually walked more than two hours a week had a 21 percent lower risk of ischemic stroke – both “borderline significant,” according to researchers.

“Physical activity, including regular walking, is an important modifiable behavior for stroke prevention,” said Jacob R. Sattelmair, M.Sc., lead author and doctoral candidate in epidemiology at Harvard School of Public Health in Boston, Mass. “Physical activity is essential to promoting cardiovascular health and reducing risk of cardiovascular disease, and walking is one way of achieving physical activity.”

More physically active people generally have a lower risk of stroke than the least active, with more-active persons having a 25 percent to 30 percent lower risk for all strokes, according to previous studies.

“Though the exact relationship among different types of physical activity and different stroke subtypes remains unclear, the results of this specific study indicate that walking, in particular, is associated with lower risk of stroke,” Sattelmair said.

Researchers followed 39,315 U.S. female health professionals (average age 54, predominantly white) participating in the Women’s Health Study. Every two to three years, participants reported their leisure-time physical activity during the past year – specifically time spent walking or hiking, jogging, running, biking, doing aerobic exercise/aerobic dance, using exercise machines, playing tennis/squash/racquetball, swimming, doing yoga and stretching/toning. No household, occupational activity or sedentary behaviors were assessed.

They also reported their usual walking pace as no walking, casual (about 2 mph), normal (2.9 mph), brisk (3.9 mph) or very brisk (4 mph).

Sattelmair noted that walking pace can be assessed objectively or in terms of the level of exertion, using a heart rate monitor, self-perceived exertion, “or a crude estimate such as the ‘talk test’ – wherein, for a brisk pace, you should be able to talk but not able to sing. If you cannot talk, slow down a bit. If you can sing, walk a bit faster.”

During 11.9 years of follow-up, 579 women had a stroke (473 were ischemic, 102 were hemorrhagic and four were of unknown type).

The women who were most active in their leisure time activities were 17 percent less likely to have any type of stroke compared to the least-active women.

Researchers didn’t find a link between vigorous activity and reduced stroke risk. The reason is unclear, but they suspect that too few women reported vigorous activity in the study to get an accurate picture and/or that moderate-intensity activity may be more effective at lowering blood pressure as suggested by some previous research.

Stroke is the third leading cause of death and a leading cause of serious disability in the United States, so it’s important to identify modifiable risk factors for primary prevention, Sattelmair said.

An inverse association between physical activity and stroke risk is consistent across genders. But there tend to be differences between men and women regarding stroke risk and physical activity patterns.

“The exact relation between walking and stroke risk identified in this study is not directly generalizable to men,” Sattelmair said. “In previous studies, the relation between walking and stroke risk among men has been inconsistent.”

The study is limited because it was observational and physical activity was self-reported. But strengths are that it was large and long-term with detailed information on physical activity, he said.

Further study is needed on more hemorrhagic strokes and with more ethnically diverse women, Sattelmair said.

The American Heart Association recommends for substantial health benefits, adults should do at least 150 minutes a week of moderate-intensity or 75 minutes a week of vigorous-intensity aerobic physical activity or a combination.

Co-authors are: Tobias Kurth, M.D., Sc.D.; Julie E. Buring, Sc.D.; and I-Min Lee, M.B.B.S., Sc.D. Individual author disclosures are on the manuscript.

The National Institutes of Health supported the study.

Birdgette McNeill

American Heart Association

Rare Form Of Stroke During Pregnancies, Post-Partum Underreported

A rare and often underreported form of stroke that involves veins instead of arteries is more common than previously thought, according to the American Heart Association’s first scientific statement on diagnosing and managing cerebral venous thrombosis (CVT).

The statement, published in Stroke: Journal of the American Heart Association, is a comprehensive review of the diagnosis, imaging, and early and long-term management (treatment) in different groups affected by CVT including children, young adults and women during pregnancy and post-partum. The stroke is caused by a clot in the dural venous sinuses, veins that drain blood from the brain toward the heart.

CVT disproportionally affects women who are pregnant or taking oral contraceptives and people 45 years and younger. The incidence of CVT during pregnancy and post-partum ranges from one in 2,500 deliveries to one in 10,000 deliveries in Western countries, according to the statement. The greatest risk periods are during the third trimester and in the first four post-partum weeks. Up to 73 percent of CVT in women occur during the time immediately after childbirth.

However, the risk of complications during future pregnancies is low, based on the writing committee’s review of data.

The committee recommends patients with suspected CVT undergo blood tests to see if they have a prothrombotic factor – an inherited or acquired factor in the blood that predisposes to blood clots. It also recommends screening patients for conditions that predispose to CVT, such as use of oral contraceptives, underlying inflammatory disease and infection.

“A predisposing condition to form clots or a direct cause is identified in about two-thirds of patients with CVT,” said Gustavo Saposnik, M.D., chair of the statement writing group and assistant professor of medicine at Saint Michael’s Hospital, University of Toronto.

“Examples include pregnancy, immediate post-partum, dehydration or infections in children, and patients taking oral contraceptives. Some of these predisposing conditions are transient and reversible.”

A blood test can determine if someone has a hereditary condition that makes their blood more likely to clot, thus increasing risk for a CVT.

The statement also highlights scenarios that cause doctors to miss or delay diagnosing CVT. Moreover, the clinical presentation may vary. For example, 30 to 40 percent of patients with CVT may develop an intracranial hemorrhage. “It’s important to distinguish a hemorrhage caused by ruptured of a brain artery from those associated with CVT. The mechanisms- and treatment – of the bleeding are quite different,” Saposnik said.

The statement recommends that patients having a brain hemorrhage with an unclear cause undergo an imaging scan of their cerebral veins assessed with an imaging test.

Headache is the most common symptom of CVT, as recorded in about 90 percent of patients in the International Study on Cerebral Venous and Dural Sinuses Thrombosis (ISCVT).

“The most common symptoms of patients with CVT include headaches that progress in severity over days or weeks, and seizures,” Saposnik said. “Some patients may develop a focal neurological deficit (weakness affecting the extremities, double vision, etc.).”

The statement includes a process to help clinicians diagnose and manage CVT:

- Clinical suspicion of CVT

- MRI (or alternative imaging for centers with lower resources)

- Confirmation of CVT

- Initiation of anticoagulation therapy (IV Heparin)

- Continue anticoagulation therapy, 3-12 months to a lifetime

- In patients with progressive neurological deterioration despite medical treatment, other options may be considered (e.g hemicraniectomy, surgery that temporarily removes a section of skull to relieve pressure on the brain, or endovascular treatment, a minimally invasive brain surgery to remove vein/dural sinus clots)

The statement includes the endorsement of several scientific organizations (e.g. ASA, AAN, SIAECV, AANS, among others).

The CVT writing team includes a multidisciplinary group of experts from the United States, Canada, Mexico, Portugal and Argentina. Co-authors are: Fernando Barinagarrementeria, M.D.; Robert D. Brown Jr., M.D., M.P.H.; Cheryl D. Bushnell, M.D., M.H.S.; Brett Cucchiara, M.D.; Mary Cushman, M.D., M.Sc.; Gabrielle deVeber, M.D.; Jose M. Ferro, M.D., Ph.D. and Fong Y. Tsai, M.D.


American Heart Association

American Stroke Association

Seniors With Insufficient Levels Of Vitamin D At Increased Risk Of Dying From Heart Disease

A new study by researchers at the University of Colorado Denver and Massachusetts General Hospital (MGH) shows vitamin D plays a vital role in reducing the risk of death associated with older age. The research, just published in the Journal of the American Geriatrics Society, evaluated the association between vitamin D levels in the blood and the death rates of those 65 and older. The study found that older adults with insufficient levels of vitamin D die from heart disease at greater rates that those with adequate levels of the vitamin.

“It’s likely that more than one-third of older adults now have vitamin D levels associated with higher risks of death and few have levels associated with optimum survival,” said Adit Ginde, MD, MPH, an assistant professor at the University of Colorado Denver School of Medicine’s Division of Emergency Medicine and lead author on the study. “Given the aging population and the simplicity of increasing a person’s level of vitamin D, a small improvement in death rates could have a substantial impact on public health.”

Older adults are at high risk for vitamin D deficiency because their skin has less exposure to the sun due to more limited outdoor activities as well as reduced ability to make vitamin D.

The study analyzed data from the Third National Health and Nutrition Examination Survey conducted by the National Center for Health Statistics. The research team analyzed vitamin D in blood samples of more than 3,400 participants that were selected to be representative of the 24 million older adults in the United States. Compared to those with optimal vitamin D status, those with low vitamin D levels were 3 times more likely to die from heart disease and 2.5 times more likely to die from any cause.

Dr. Ginde says the findings suggest that current daily recommendations of vitamin D may not be enough for older adults to maintain optimal health. The research team has applied for research funding from the National Institutes of Health to perform a large, population-based clinical trial of vitamin D supplementation in older adults to see if it can improve survival and reduce the incidence of heart disease.

“Confirmation of these results in large randomized trials is critically important for advancing public health,” says Carlos Camargo, MD, DrPH, of the MGH Department of Emergency Medicine, the senior author of the study and an associate professor of medicine at Harvard Medical School.

The study looking at elderly death rates is the second of two studies by the same team of researchers on vitamin D and general health. The first study, published in Archives of Internal Medicine earlier this year, identified vitamin D as playing a significant role in boosting the immune system and warding off colds and flu.

“Vitamin D has health effects that go beyond strong bones,” says Ginde. “It’s likely that it makes a vital contribution to good health.”

Jacque Montgomery, University of Colorado Denver

Massachusetts General Hospital

Phase 1 Trial Of Whole-parasite Malaria Vaccine To Begin

In a move that highlights the strength of public-private collaboration in tackling international health challenges, the Maryland-based company Sanaria Inc., with support from the PATH Malaria Vaccine Initiative (MVI), has initiated a Phase 1 clinical trial-the first tests in adult volunteers-of its unique malaria vaccine candidate. Unlike other malaria vaccine candidates, Sanaria’s approach deploys a weakened form of the whole malaria parasite harvested from irradiated mosquitoes instead of small portions of the parasite.

Having met the US Food and Drug Administration’s (FDA) rigorous safety, sterility, purity, potency, and reproducibility requirements for testing in humans, Sanaria’s vaccine candidate is to be assessed in healthy US volunteers at two sites in Maryland-the US Naval Medical Research Center Clinical Trials Center in Bethesda and the Center for Vaccine Development at the University of Maryland School of Medicine in Baltimore. Recruitment has begun for the safety and efficacy study that will involve some 104 volunteers, with inoculation of the first groups expected to begin in mid-May.

“Initiation of this trial expands the spectrum of malaria vaccines in clinical development today,” said Dr. Christian Loucq, Director of MVI. “This trial marks a major achievement in a collaborative development effort that aims to determine whether Sanaria’s vaccine candidate is safe and effective.”

While most malaria vaccines in clinical development consist of recombinant or genetically engineered proteins that represent small portions of the parasite, Sanaria’s Plasmodium falciparum sporozoite vaccine candidate contains a weakened form of the entire malaria parasite. While unique to the malaria vaccine field, such live vaccines are used for other diseases including smallpox, polio, and measles. When the attenuated parasite is given to individuals, they are expected to become immune to malaria and not get sick.

Evidence that the Sanaria approach has the potential to confer high levels of protection against malaria comes from previous studies in which volunteers were exposed to the bites of mosquitoes harboring weakened parasites. While the technological challenges associated with translating this approach into an effective and safe vaccine based on live parasites had been widely viewed as insurmountable, Sanaria has developed novel technologies and constructed a unique manufacturing facility that allows scientists to manufacture the candidate vaccine.

“The Sanaria team has been able to systematically overcome obstacle after obstacle in a remarkably short time. I look forward to working with the rest of the team to bring this vaccine over the finish line and into widespread use to prevent the devastating illnesses and deaths caused by malaria,” said Adel Mahmoud, former president of Merck Vaccines and member of Sanaria’s board of directors.

Ultimately, the measure of success will be a safe, effective licensed vaccine that is widely deployed to prevent malaria, especially in African children.

“The first clinical trial of Sanaria’s candidate malaria vaccine is a watershed event. It is the culmination of a remarkable translational research effort by Sanaria directed at realizing the dream of a practical malaria vaccine preparation based upon whole parasites,” states Michael Good, Director of the Queensland Institute of Medical Research.

Myron M. Levine, Director of the University of Maryland School of Medicine’s Center for Vaccine Development notes, “Development of Sanaria’s vaccine candidate is based in part on the findings from parallel studies conducted in the early 1970s by teams at the Center for Vaccine Development and the Naval Medical Research Center-findings that were never translated into a vaccine development effort because the task was considered to be impossible.”


Diet-Exercise Combo Best For Obese Seniors

For obese seniors, dieting and exercise together are more effective at improving physical performance and reducing frailty than either alone.

The research, by a team at Washington University School of Medicine in St. Louis, is reported March 31 in The New England Journal of Medicine.

Older adults who are obese face severe health risks, including high blood pressure, heart disease and diabetes, which can be compounded by a lack of mobility.

“We wanted to tease apart the effects of dieting and exercise in older people who are obese,” says principal investigator Dennis T. Villareal, MD, adjunct associate professor of medicine at Washington University School of Medicine in St. Louis. “In older adults, obesity exacerbates declines in physical performance and leads to frailty, impaired quality of life and increases in nursing home admissions. Given the increasing prevalence of obesity even among older people, it is important to find ways to combat the problem and help seniors remain healthier and more independent.”

In this study, Villareal and his colleagues evaluated the effects of dieting and exercise in more than 100 obese seniors over a one-year period. Although weight loss alone and exercise alone improved physical function by about 12 percent and 15 percent, respectively, neither was as effective as diet and exercise together, which improved physical performance by 21 percent.

The investigators used the Physical Performance Test, a test that evaluates an individual’s ability to perform tasks, such as walking 50 feet, putting on and removing a coat, standing up from a chair, picking up a penny, climbing a flight of stairs and lifting a book.

In addition, the researchers evaluated peak oxygen consumption during exertion with treadmill walking. On that test, obese elderly people who both dieted and exercised improved 17 percent from their baseline. The diet-only group showed a 10 percent gain, and the exercise-only group improved about 8 percent.

All subjects in the study were over 65, with some as old as 85 when the study began. Their average age was about 70. Volunteers were randomly assigned to one of four groups. One set of seniors was placed on a low-calorie diet to help them lose weight. Members of a second group attended exercise sessions three times a week, doing balance work, resistance training and aerobic exercise. A third group combined both the low-calorie diet and the exercise. The last group made no changes in diet or exercise habits.

All subjects had medically significant obesity, defined as having a body mass index (BMI) of 30 or more. BMI measures the relationship between a person’s height and weight.

At the study’s outset, participants had evidence of frailty and impaired physical function based on their Physical Performance Test and on measures of their peak aerobic capacity using an exercise stress test and a questionnaire about their physical function.

Villareal and his team also surveyed study subjects about their quality of life, and again, those in the combined diet-exercise group had the biggest improvements. Their scores improved by 15 percent, compared to 14 percent in the diet-only group and 10 percent in the exercise-only group. By every measure, strength, balance and gait all showed the most consistent improvement in the diet-exercise group.

“In older, obese people, it may be more important to improve physical function and quality of life, rather than to reverse or treat risk factors for cardiovascular disease,” says Villareal, now chief of geriatrics at the New Mexico Veterans Affairs Health Care System and professor of medicine at the University of New Mexico School of Medicine, both in Albuquerque. “Combining exercise and weight loss isn’t designed so much to extend their life expectancy as it is to improve their quality of life during their remaining years and to help seniors avoid being admitted to a nursing home.”

There is some debate, however, about whether it’s good for elderly people to lose weight, even if they are obese. Some studies have found an association between weight loss in seniors and mortality risk, but Villareal says many of those studies did not distinguish between voluntary weight loss and involuntary weight loss that may be related to illness.

But even if voluntary weight loss carries no significant risk of shortening life, another potential drawback is that when older people lose fat, they also tend to lose muscle and bone.

In this study, the researchers did find slight reductions in lean body mass and bone mineral density among those who lost weight, but the decreases were smaller in the combined diet-exercise group than in those who dieted or exercised alone. The diet-exercise group participants lost 3 percent of their lean body mass, with a 1 percent bone mineral loss in the key area of the hip. Those who only dieted lost 5 percent of their lean body mass and 3 percent in bone mineral density at the hip.

Just as in younger people, the prevalence of obesity has increased in the elderly. About 20 percent of people 65 and older are obese, and that is expected to continue rising as more baby boomers become senior citizens. Elevated weight is known to be associated with impairments in daily living, limitations in mobility and an increased risk for physical decline and frailty.

“Although losing weight is beneficial and exercise also is good, when seniors do both, they get a greater improvement,” he says.

Villareal DT, Chode S. Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, Napoli N, Qualls C, Shah K. Weight loss, exercise or both and physical function in obese older adults, The New England Journal of Medicine, vol. 364(13), pp. 1218-1229. March 31, 2011.

This work was supported by grants from the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health and by the Foundation for Physical Therapy.

Source: Washington University in St. Louis

Levator Trauma Is Associated With Pelvic Organ Prolapse

UroToday – It is generally accepted that vaginal childbirth is an important factor in the pathogenesis of female pelvic organ prolapse. Large epidemiological studies leave little doubt that childbirth can impair pelvic organ support (1). This study was designed to quantify the role of a recently identified aetiological factor, i.e, direct trauma, to the insertion of the puborectalis muscle on the inferior pubic ramus. Such trauma is common (2, 3) and clearly linked to vaginal delivery (4, 5).

In our population the presence of an identified levator defect approximately doubled the risk of significant prolapse (RR 1.9, CI: 1.7-2.1). The prevalence of levator avulsion was about four times greater in women with significant clinically diagnosed pelvic organ prolapse (POP-Q Stage 2 or higher) than in women without prolapse. The association was strongest for the anterior and central compartments, and patients with bilateral avulsion were particularly likely to suffer from uterine prolapse (relative risk of 7.1).

Our findings are consistent with results recently obtained by magnetic resonance imaging where patients with prolapse were more likely to have major levator ani defects than controls (55% compared with 16%), with an adjusted odds ratio of 7.3 (95% confidence interval 3.9-13.6) (6). When we analysed our data to allow for comparison of data, we obtained an unadjusted odds ratio of 6.1 (CI 4.0-9.3), with 150/415 (36%) of prolapse patients showing an avulsion compared to 31/366 (8%) without significant prolapse.

The association between prolapse and levator trauma is not surprising given that avulsion injury has a marked effect on hiatal dimensions, distensibility and contractility, and effect that has been shown by palpation (7), instrumented speculum (6) and ultrasound imaging (8). Together, these data further strengthen the aetiological link between childbirth and female pelvic organ prolapse. It now seems very likely that delivery-related major levator trauma is a significant factor in the pathogenesis of prolapse. This is particularly obvious for cystocele and uterine prolapse.

Undoubtedly however, levator avulsion is not the only mechanism by which pelvic floor muscle function and pelvic organ support may be impaired. Childbirth clearly leads to an enlargement of the levator hiatus, even if avulsion injury does not ensue (9), and such over-distension of an intact muscle may equally predispose to prolapse. Finally, it is very likely that congenital factors and/ or fascial trauma play a role in many women, even if both may be much more difficult to identify than muscular trauma.

The identification of a major modifiable risk factor opens up novel opportunities for prevention. Levator avulsion is likely to be a useful intermediate outcome variable for intervention studies. Any change in clinical practice resulting in a reduced prevalence of levator avulsion would be expected to have a positive effect on the prevalence of significant prolapse later in life. We are currently undertaking two randomized controlled trials aimed at reducing the incidence of levator avulsion in childbirth, using antenatal intervention strategies.

One of the more obvious weaknesses of our study is the fact that it was undertaken in a urogynaecological population. While the majority of our patients did not complain of symptoms of prolapse, they were certainly not asymptomatic as they presented with other urogynaecological complaints. It remains to be shown to what extent these results are applicable to the general population. Furthermore, operators were not blinded against prolapse findings when they assessed for levator defects. We do not expect this bias to be significant: in an unrelated study examining the repeatability of the digital detection of levator trauma, the association between prolapse and defects was in fact stronger for the examiner who was blinded against clinical data than in the operator who undertook the levator assessment immediately after examining for prolapse (unpublished own data). However, we can not exclude that bias may have contributed to the association observed in this population.

It would be preferable to confirm findings by using a study design that separates prolapse assessment and the diagnosis of levator injury, allowing for blinding of operators. In addition, longitudinal cohort studies need to be undertaken in order to monitor the medium- term effect of levator trauma on pelvic organ support after childbirth, and to ascertain the role of avulsion injury in recurrence after reconstructive surgery.


1. DeLancey J. The hidden epidemic of pelvic floor dysfunction: achievable goals for improved prevention and treatment. Am J Obstet Gynecol 2005;192:1488- 95.

2. Kearney R, Miller J, Ashton-Miller J, Delancey J. Obstetric factors associated with levator ani muscle injury after vaginal birth. Obstet Gynecol 2006;107(1):144-9.

3. Dietz HP, Steensma AB. The prevalence of major abnormalities of the levator ani in urogynaecological patients. BJOG: An International Journal of Obstetrics & Gynaecology 2006;113(2):225-30.

4. Dietz H, Gillespie A, Phadke P. Avulsion of the pubovisceral muscle associated with large vaginal tear after normal vaginal delivery at term. Aust NZ J Obstet Gynaecol 2007;47:341-4.

5. Lien KC, Mooney B, DeLancey JO, Ashton-Miller JA. Levator ani muscle stretch induced by simulated vaginal birth. Obstet Gynecol 2004;103(1):31-40.

6. DeLancey J, Morgan D, Fenner D, et al. Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstetrics & Gynecology 2007;109(2):295-302.

7. Dietz HP, Shek C. Levator Avulsion and Grading of Pelvic Floor Muscle Strength. Int Urogynecol J 2008;in print.

8. Abdool Z, Shek K, Dietz H. The effect of levator avulsion on hiatal dimensions and function. Neurourol Urodyn 2008;27:in print.

9. Dietz H, Lanzarone V. Levator trauma after vaginal delivery. Obstet Gynecol 2005;106:707-12.

HP Dietz PhD, and JM Simpson PhD, as part of Beyond the Abstract on UroToday. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.

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