Stem Cell Obstacles

“There are still a number of major hurdles in the path of stem cell research today that are preventing the routine application of the technology in regenerative medicine.” So say UK scientists writing in a forthcoming issue of the International Journal of Biotechnology.

In an article entitled, “Blazing the trail from stem cell research to regenerative medicine”, Jane Bower of the ESRC Innogen Centre, at University of Edinburgh, and colleagues highlight some of the recent advances in stem cell science. They suggest that research in this area holds promise for applications in regenerative medicine, but point out that technical and ethical remain to be addressed. The researchers also discuss the issue of how to patent stem cell discoveries and to make them commercially viable.

Stem cells are immature cells that can replicate rapidly and then mature into the different cells needed around the body to build tissues in the skin, liver, heart, bone, brain, blood cells, nerves. They are present only in limited quantities in adults but are present in huge numbers in embryonic tissue. Human embryonic stem cells are currently the most promising source for therapeutic purposes, but their use has ethical implications.

Stem cell research holds great promise in medicine. Advocates hope that the work will lead to important therapies for tackling major degenerative diseases, such as Parkinson’s, Alzheimer’s, stroke, heart disease, diabetes, cancer and arthritis. There are also the possibilities of using stem cells to treat debilitating injuries of the spinal cord and other structural injuries. Indeed, the recent case of the trachea engineered to avoid organ rejection by using a patient’s own stem cells is a prominent and early success. Stem cells will also have applications in discovering and testing new drugs.

“Technical solutions may involve the use of human embryos and this has created barriers to the use of the technology in a number of countries,” Bower and colleagues say, “There is already a need for the progressive development of appropriate legal and regulatory frameworks to allow both the scientific and clinical research to move forward.” The team adds that, “Although public acceptability of the technology is by no means universal, it does not at present appear that therapeutic applications are likely to meet with wholesale rejection.”

The researchers explain that while there remain technical obstacles to be overcome in stem cell research, Western scientists are not the only ones working on advancing this field. Scientists in China, South Korea, and India are also taking steps forward, although revelations of scientific fraud have led to additional negative publicity.

Nevertheless, the team believes that if a high level of routine success were achieved outside the West, then this might have a positive impact on the public demand for stem cell therapies in the West and so create the political pressure necessary to address the regulatory, legal, and ethical issues sooner rather than later.

Inderscience
inderscience

Zebrafish May Help Solve Ringing In Veterans’ Ears

Ernest Moore, an audiologist and cell biologist at Northwestern University, developed tinnitus — a chronic ringing and whooshing sound in his ears — twenty years ago after serving in the U.S. Army reserves medical corps. His hearing was damaged by the crack of too many M16 rifles and artillery explosions. He suspects his hearing also suffered from hunting opossum with rifles as a kid on his grandmother’s farm in Tennessee.

Ever since his ears began ringing, Moore has been researching a cure. He’s at the forefront of just a small band of such scientists in the country. There’s a lot riding on his work.

Half of the soldiers returning from Iraq and Afghanistan exposed to explosive devices suffer from tinnitus. The major cause is exposure to loud noises, which can damage and destroy hair cells of the inner ear. It’s the number one war-related disability.

Nearly 400,000 troops collected disability for service-related tinnitus in 2006, which cost $539 million in 2006. The number climbs nearly 20 percent each year. It could hit $1 billion by 2011, according to the American Tinnitus Association.

An additional 12 million Americans have tinnitus severe enough to seek medical attention. In about two million of those cases, patients are so debilitated they can’t function normally.

Despite the widespread suffering, there has only been a paltry $3 million allotted for public and private research. As a tinnitus researcher, Moore feels like a cross between Rodney Dangerfield and Sisyphus.

It’s been tough to snare research money from the small purse and hard to garner respect for tinnitus. “Ears don’t bleed from tinnitus,” Moore explained. “It’s a hidden problem. It’s not obvious and dramatic like a heart attack or cancer — although it torments its sufferers.” Only one out of ten grant proposals he submits each year have been funded.

The research itself is challenging because Moore can’t ask mice and rats if their ears are ringing. Now, he’s working with zebrafish (yes, they do have ears, which are remarkably similar to humans’ ears.) He’s been able to cause ringing in their ears — he thinks — by exposing them to certain drugs and tracking their erratic swimming on video. Moore then looks at the cells in their ears to see if the electrical firing has increased, an early sign of damage and tinnitus. His early findings show an increased firing.

Then Moore attempts to block this effect with drugs to return the cells to their normal activity. In preliminary research, it appears the drugs he has tested do slow down the increased electrical firing or tinnitus-like behavior of the hair cells in the ear.

Moore is beginning to meet with doctors to discuss launching a clinical trial to test these drugs for patients with tinnitus.

“If these drugs are found to be safe — and some are already on the market for other uses — and if they are found to have efficacy in humans, then they might be used to treat an individual’s tinnitus,” Moore said.

“If the hair cell is not totally damaged — just beginning to break down, and you administer these drugs, you might be able to prevent it from further damage and interfere with the cells’ ability to generate tinnitus,” he explained.

Tinnitus finally will begin to get some respect in April when The Department of Defense 2008 Appropriations Bill will open up $50 million in new research funding for tinnitus related to service in the armed forces. Ernest Moore has applied to launch the clinical trial with the drugs he has used with the zebrafish.

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Source: Marla Paul

Northwestern University

ParkwayHealth’s Living Donor Liver Transplant Program Continues To Meet Patient Demands

ParkwayHealth, Asia’s leading healthcare provider with the largest network of private hospitals and healthcare services headquartered in Singapore and the first in Asia to perform a living donor liver transplant (LDLT) in 2002, reports that its Gleneagles Hospital has performed over one hundred successful LDLT procedures to date. With the full program in place, the hospital expects to perform about 50 procedures annually.

“Since its inception, the LDLT program has provided an exceptional, quality-focused program, with milestones that include the first pediatric and adult living transfers in Asia,” says Thomas Johnsrud, consultant for Parkway Health North America.

LDLT is a procedure in which a diseased liver is replaced with a segment of liver from a healthy human donor, usually a sibling or close family member. Living donor liver transplantation can be performed on anyone with end-stage liver disease regardless of the original cause of their disease.

“The success of liver transplantation at Gleneagles has resulted in a dramatic increase in the number of patients who are now being considered for this operation,” says Johnsrud, noting that in 2007, there were 17,440 patients waiting for a liver transplant in the United States. “The number of cadaver donors available for transplantation was simply insufficient, a factor which led to the development of the LDLT program.”

Gleneagles program director Tan Kai-Chah, M.D., a pioneer in the LDLT procedure, has performed more than 500 liver transplants in Britain, Singapore and Malaysia. He leads the team which comprises experts from various specialties, with expertise and extensive experience in major hepatobiliary and liver transplantation surgery.

With an ongoing and increasing shortage of cadaver livers, transplant centers in Asia have adopted living donation as a partial solution to this shortage. Individuals now recognize that by donating a portion of their liver to a relative, friend or co-worker, they can make give the gift of life.

About ParkwayHealth

ParkwayHealth is Asia’s leading healthcare provider with the largest network of private hospitals and healthcare services headquartered in Singapore. Parkway Holdings Limited (PHL) owns Parkway Hospitals Singapore Pte Ltd which runs East Shore Hospital, Gleneagles Hospital, Mount Elizabeth Hospital and ParkwayHealth Day Surgery and Medical Centre. Over 1500 accredited medical specialists support Parkway’s clinical programs in Heart and Vascular, Neuroscience, Oncology, Musculoskeletal, Transplant and Cellular Therapy, Women and Children, Chronic Disease Management and Surgery. Visit parkwayhealth or parkwayholdings.

ParkwayHealth

Hazardous Chemicals From Scented Laundry Products Released Through Dryer Vents

The same University of Washington researcher who used chemical sleuthing to deduce what’s in fragranced consumer products now has turned her attention to the scented air wafting from household laundry vents.

Findings, published online this week in the journal Air Quality, Atmosphere and Health, show that air vented from machines using the top-selling scented liquid laundry detergent and scented dryer sheet contains hazardous chemicals, including two that are classified as carcinogens.

“This is an interesting source of pollution because emissions from dryer vents are essentially unregulated and unmonitored,” said lead author Anne Steinemann, a UW professor of civil and environmental engineering and of public affairs. “If they’re coming out of a smokestack or tail pipe, they’re regulated, but if they’re coming out of a dryer vent, they’re not.”

The research builds on earlier work that looked at what chemicals are released by laundry products, air fresheners, cleaners, lotions and other fragranced consumer products. Manufacturers are not required to disclose the ingredients used in fragrances, or in laundry products.

For the new study, which focuses on chemicals emitted through laundry vents, researchers first purchased and pre-rinsed new, organic cotton towels. They asked two homeowners to volunteer their washers and dryers, cleaned the inside of the machines with vinegar, and ran full cycles using only water to eliminate as much residue as possible.

At the first home, they ran a regular laundry cycle and analyzed the vent fumes for three cases: once with no products, once with the leading brand of scented liquid laundry detergent, and finally with both the detergent and a leading brand of scented dryer sheets. A canister placed inside the dryer vent opening captured the exhaust 15 minutes into each drying cycle. Researchers then repeated the procedure with a different washer and dryer at a second home.

Analysis of the captured gases found more than 25 volatile organic compounds, including seven hazardous air pollutants, coming out of the vents. Of those, two chemicals – acetaldehyde and benzene – are classified by the Environmental Protection Agency as carcinogens, for which the agency has established no safe exposure level.

“These products can affect not only personal health, but also public and environmental health. The chemicals can go into the air, down the drain and into water bodies,” Steinemann said.

The researchers estimate that in the Seattle area, where the study was conducted, acetaldehyde emissions from this brand of laundry detergent would be equivalent to 3 percent of the total acetaldehyde emissions coming from automobiles. Emissions from the top five brands, they estimate, would constitute about 6 percent of automobiles’ acetaldehyde emissions.

“We focus a lot of attention on how to reduce emissions of pollutants from automobiles,” Steinemann said. “And here’s one source of pollutants that could be reduced.”

The project’s website also includes letters from the public reporting health effects from scented consumer products. Steinemann says that people’s reports of adverse reactions to fragranced air coming from laundry vents motivated her to conduct this study.

Steinemann recommends using laundry products without any fragrance or scent.

Co-authors are Lisa Gallagher and Amy Davis at the UW, and Ian MacGregor at Battelle Memorial Institute.

Better Stroke Survival Rates For African-Americans

A study just published shows that African Americans have a better survival rate compared to whites after being hospitalized for a stroke. This conclusion contradicts prevailing wisdom and is one piece in a growing body of evidence that points to the important role that patients – and the decision they and their families make in terms of treatment – may play on mortality rates.

The study found that – after adjusting data for variables such as age, socioeconomic status, and risk factors – that African Americans who were hospitalized for acute ischemic stroke had a significantly lower mortality rate than whites. The survival advantage was most pronounced early after the stroke but persisted for up to one year. The study also found that African Americans were also more likely during their hospitalization to have received more aggressive treatment measures, such as kidney dialysis, a tracheostomy, or cardiopulmonary resuscitation. They were also less likely to use hospice care. These results were published in the Annals of Internal Medicine.

“These results fly in the face of conventional wisdom that says that black patients with strokes have worse outcomes,” said University of Rochester Medical Center (URMC) neurologist Robert Holloway, M.D., M.P.H. a co-author of the study. “Even though we do not know the exact reasons for these differences, these data highlight the potential importance of treatment intensity, and the expression of patient preference for different treatments on survival and mortality. This is not such a far-fetched idea for physicians who take care of a lot of stroke patients.”

“We know that African Americans have a higher prevalence of stroke and higher risk factors for stroke,” said Ying Xian, M.D., Ph.D., a former graduate student in Health Services Research and Policy with URMC Department of Community and Preventive Medicine and now a fellow with the Duke Clinical Research Institute and co-author of the study. “But this data shows that African Americans have lower mortality rates than whites. It also shows that African Americans are more likely to be treated aggressively and we suspect that this may have an impact on their mortality outcomes.”

The study used data from the New York State Statewide Planning and Research Cooperative System, a reporting system that collects detailed information on every hospital and emergency department admission in the state. They compiled information for all non-Hispanic blacks and non-Hispanic whites age 18 and older who were admitted to a hospital with a diagnosis of acute ischemic stroke in 2005 and 2006.

The researchers used a novel statistical approach to minimize the difference between two pools of black and white patients in terms of demographic profiles, co-morbidities, and the type of hospital where they received their care. They then looked at mortality rates for several incremental periods beginning at 7 days and up to a year after the stroke and what life-sustaining interventions the patients received during their hospitalization. The authors found that over the course of the year African American patients had a statistically lower rate of mortality and at the same time were more likely to receive aggressive life-sustaining treatments.

While the data used for the study does not illustrate the role of patient preference – either expressed intent or in the form of do not resuscitate orders, health care proxies, or living wills – or the decisions made by family member on their behalf, the authors believe the evidence indicates that there might be a link between the treatment decisions made by patients and their families when seriously ill with stroke and survival rates.

“Although we don’t show any causal relationship, the association of lower risk of death and increased use of life-sustaining interventions is actually very consistent with the idea that preference sensitive end-of-life care may have an important impact on short-term mortality,” said Holloway. “We were unable to measure health or quality of life in those patients who survived, which is a critically important question. We also need much more research on ways to measure the quality of the decision process itself to make sure that the treatments patients receive are consistent with their underlying values and preferences.”

“Even though people who receive aggressive life-sustaining care have lower mortality it does not mean they have better quality of care or quality of life,” said Xian. “Mortality is important measure but not only measure.”

Notes:

Other authors of the study include Katia Noyes, Ph.D., M.P.H.; Manish N. Shah, M.D., M.P.H.; and Bruce Friedman, Ph.D., M.P.H. with URMC. The study was supported by funding from the American Heart Association.

Source:
Mark Michaud
University of Rochester Medical Center

Older Adults With Depressive Symptoms Are More Likely To Become Cognitively Impaired

Older adults with depressive symptoms are more likely than those without depression to develop mild cognitive impairment (MCI) within six years, according to a study conducted by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.

The greater the degree of depression, the more likely the impairment, the researchers found.

“This is important, because mild cognitive impairment often precedes dementia,” notes lead author Deborah Barnes, PhD, MPH, a mental health researcher at SFVAMC. Approximately 50 percent of patients diagnosed with MCI go on to develop dementia within three years, according to the study authors.

The study also found no correlation between depression and vascular disease — a significant finding, say the authors, because other researchers have hypothesized that vascular disease might lead to both depression and cognitive impairment by causing inadequate blood flow to different brain structures. “We found no evidence to support that hypothesis,” reports Barnes, who is also an assistant professor of psychiatry at UCSF.

The study appears in the March, 2006 issue of Archives of General Psychiatry.

The researchers looked at 2,220 participants in the Cardiovascular Health Study, a longitudinal prospective study of adults 65 and older living in four American communities that is sponsored by the National Heart, Lung, and Blood Institute. The researchers measured the subjects’ depressive symptoms using a standard depression scale. Six years later, the subjects were assessed for MCI by a team of dementia experts.

Ten percent of subjects with no depressive symptoms went on to develop MCI, and 13.3 percent of subjects with low depressive symptoms did. In contrast, 19.7 percent of subjects with moderate to high depression developed MCI after six years — nearly twice the rate of subjects with no depressive symptoms.

The findings were consistent among all subgroups in the study — men and women, younger and older, with and without vascular disease, and regardless of education level.

One major implication of the study, according to Barnes, is that family members and health care providers should pay attention when an older person seems newly depressed. “Even if they don’t have cognitive impairment at that time, our study suggests that you probably want to keep an eye on them,” she says. “Depression might be an early sign of neurodegeneration — in fact, it might be the first symptom that a family member notices.”

Kristine Yaffe, MD, chief of geriatric psychiatry at SFVAMC and the principal investigator of the study, says the next step is to investigate whether treating older adults with newly diagnosed depressive symptoms might be effective in preventing the development of MCI. “Perhaps getting a family member in for early treatment would make a difference,” she speculates. “We don’t know the answer yet, but I think it’s important to evaluate.” Yaffe is also associate professor of psychiatry, neurology, and epidemiology at UCSF.

Barnes says she would also like to see other researchers investigate the reasons for the association between depression and MCI. “If vascular disease is not the mechanism, what is?” she asks. “One theory is that people who are undergoing stress or experiencing depression often have elevated levels of the stress hormone cortisol. There is growing evidence that this may lead directly to brain damage in the hippocampus,” a part of the brain that plays a significant role in memory and Alzheimer’s disease. “It would be good to find out,” she concludes.

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Co-authors of the study were George S. Alexopoulos, MD, of Cornell University; Oscar L. Lopez, MD, of the University of Pittsburgh School of Medicine; and Jeff D. Williamson, MD, MHS, of Wake Forest University School of Medicine.

The research was supported by grants from the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the National Alliance for Research on Schizophrenia and Depression.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.

Contact: Steve Tokar
steve.tokarncire
University of California – San Francisco

CDC Recognizes 73 Alabama Water Systems For Water Fluoridation Quality, USA

The Alabama Department of Public Health announces that 73 Alabama public water systems
will receive Water Fluoridation Quality Awards from the U.S. Centers for Disease Control and
Prevention.

Fluoridation is the adjustment of fluoride in the water to a level that is optimal for preventing
tooth decay. The award recognizes those communities that maintained a consistent level of
optimally fluoridated water throughout 2007. According to CDC’s Water Fluoridation Reporting
System, Alabama has 121 public water systems that provide adjusted fluoride to their water
supplies.

“We are very pleased to announce that Alabama water systems have shown marked increases
in maintaining optimal fluoridation in the past three years,” said Dr. Donald Williamson, state
health officer. The number of systems which have received this honor grew from just 4 in 2005,
to 53 in 2006, to 73 in 2007.

The CDC recognized community water fluoridation as one of 10 great public health
achievements of the 20th Century. CDC recommends water fluoridation as a safe, effective and
inexpensive method of preventing decay; every $1 invested in fluoridation saves approximately
$38 in costs for dental treatment. In addition, studies have shown that tooth decay is prevented
among all age groups, not just children.

More than 184 million people, or 69.2 percent of the United States population served by public
water supplies, currently drink water with optimal fluoride levels for preventing decay.

“Our latest national and state fluoridation statistics show us that we have made significant
progress towards our national objective of reaching 75 percent of U.S. residents,” stated Dr.
William R. Maas, DDS, MPH, director of the CDC Division of Oral Health. “This is largely due to
the efforts of the states and communities who are receiving these quality awards for fluoridation.
Alabama Department of Public Health’s county environmental and oral health staff, Alabama
Department of Environmental Management staff, local water plant staffs and CDC made this
achievement possible by submitting or collecting data to report in the Water Fluoridation
Reporting System.

For more information contact Shellie Lyles, Oral Health Program, Alabama
Department of Public Health, at (334) 206-3896 or visit adph/oralhealth/.

Alabama
Department of Public Health

CDC Recognizes 73 Alabama Water Systems For Water Fluoridation Quality, USA

The Alabama Department of Public Health announces that 73 Alabama public water systems
will receive Water Fluoridation Quality Awards from the U.S. Centers for Disease Control and
Prevention.

Fluoridation is the adjustment of fluoride in the water to a level that is optimal for preventing
tooth decay. The award recognizes those communities that maintained a consistent level of
optimally fluoridated water throughout 2007. According to CDC’s Water Fluoridation Reporting
System, Alabama has 121 public water systems that provide adjusted fluoride to their water
supplies.

“We are very pleased to announce that Alabama water systems have shown marked increases
in maintaining optimal fluoridation in the past three years,” said Dr. Donald Williamson, state
health officer. The number of systems which have received this honor grew from just 4 in 2005,
to 53 in 2006, to 73 in 2007.

The CDC recognized community water fluoridation as one of 10 great public health
achievements of the 20th Century. CDC recommends water fluoridation as a safe, effective and
inexpensive method of preventing decay; every $1 invested in fluoridation saves approximately
$38 in costs for dental treatment. In addition, studies have shown that tooth decay is prevented
among all age groups, not just children.

More than 184 million people, or 69.2 percent of the United States population served by public
water supplies, currently drink water with optimal fluoride levels for preventing decay.

“Our latest national and state fluoridation statistics show us that we have made significant
progress towards our national objective of reaching 75 percent of U.S. residents,” stated Dr.
William R. Maas, DDS, MPH, director of the CDC Division of Oral Health. “This is largely due to
the efforts of the states and communities who are receiving these quality awards for fluoridation.
Alabama Department of Public Health’s county environmental and oral health staff, Alabama
Department of Environmental Management staff, local water plant staffs and CDC made this
achievement possible by submitting or collecting data to report in the Water Fluoridation
Reporting System.

For more information contact Shellie Lyles, Oral Health Program, Alabama
Department of Public Health, at (334) 206-3896 or visit adph/oralhealth/.

Alabama
Department of Public Health

Studies On Genetics And Stem Cell Research, Stents Included In Top10 Research Advances, American Heart Association

Several new studies on genetics and stem cell research, along with studies that continue to debate the use of stents to clear coronary artery blockages are among the top research advances in heart disease and stroke for 2007, said Daniel W. Jones, M.D., president of the American Heart Association.

Other major milestones include a study that may change the way lives are saved using a new way to do cardiopulmonary resuscitation.

The American Heart Association in 1996 began compiling an annual list of the top 10 major advances in heart disease and stroke research and continues to highlight influential research annually.

Achievements in 2007 include:

* 1. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Genome wide association studies identify genes (strands of DNA) which may cause specific diseases and represent a powerful approach in identifying genes involved in common human diseases. This large-scale genome-wide association (GWA) study found consistent and replicable genetic markers of several complex diseases of adulthood, including atherosclerotic heart disease. Study authors said their analysis of some 17,000 people for seven common familial diseases (bipolar disorder, coronary artery disease, Crohn’s disease, hypertension, rheumatoid arthritis, type 1 diabetes, and type 2 diabetes) confirms previously identified loci (DNA closely linked to genes that may identify a trait of a particular disease) and provides strong evidence for many novel disease susceptibility genes.

Source: Nature, June 7, 2007; Nature 2007. 447:661-78; nature/.

Funding: Wellcome Trust was the principle funding source of this study.

*
2. Genomewide association analysis of coronary artery disease

This study included a joint analysis of two genomewide association studies of coronary artery disease. Researchers used the genetic patterns of the persons (cases) with coronary artery disease (CAD) from the Wellcome Trust Case Control Consortium study (described above) and tried to replicate the genetic patterning for CAD in another genomewide association study – the German MI [Myocardial Infarction] Family Study. Results identified several genetic loci that, individually and in aggregate, substantially affect the risk of developing coronary artery disease.

Source: New England Journal of Medicine, Aug. 2, 2007; N Engl J Med 2007. 357:443-453; nejm/.

Funding: Grants from the Wellcome Trust, the National Genome Research Network 2 of the German Federal Ministry of Education and Research and the Cardiogenics project of the European Union supported this study.

*
3. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-Kanto): an observational study

This work represents the first meaningful chance to improve cardiopulmonary resuscitation (CPR) in more than 50 years. Results indicate chest compression-only resuscitation by bystanders may be the preferable approach to resuscitation for adult patients with witnessed out-of-hospital cardiac arrest, especially those with apnea, shockable rhythm or short periods of untreated arrest.

Source: The Lancet, March 17, 2007. The Lancet 2007; 369:920-926; thelancet/.

Funding: Grants from the Laerdal Foundation of Acute Medicine, Norway and the Ministry for Health, Labour and Welfare, Japan supported this study.

*
4. Implementation of a statewide system for coronary reperfusion

This study found that a statewide program focused on regional systems for quickly treating ST-elevation myocardial infarctions (STEMI – heart attacks in which the coronary artery is completely blocked) can significantly improve quality of care. The research sets the stage for collaborative, non-competitive care for patients of a region, expanding door-to-balloon initiatives into the community for a systems approach. The American Heart Association’s Mission: Lifeline program, created to establish systems to provide emergency care for STEMI patients, promotes this strategy for improving patient care.

Source: Journal of the American Medical Association, Nov. 28, 2007; JAMA 2007; 298(20);2371-23809; jama/. This study was also presented at the American Heart Association Scientific Sessions 2007.

Funding: Blue Cross and Blue Shield of North Carolina supported this study.

*
5. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP)

This is the first major trial to document that a reduced sodium intake lowers the risk of clinical cardiovascular disease outcomes, not just blood pressure.

Source: British Medical Journal, April 20, 2007; BMJ 2007;334;885; bmj/.

Funding: The National Heart, Lung and Blood Institute, National Institutes of Health supported this study.

*
6. Optimal medical therapy with or without PCI for stable coronary artery disease (COURAGE)

This study compared the initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) vs. optimal medical therapy alone in reducing the risk of cardiovascular events. The authors concluded that, as an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction or other major cardiovascular events when added to optimal medical therapy.

Source: New England Journal of Medicine, April 12, 2007; N Engl J Med 2007; 35;(15);1503-16; nejm/. .

Funding: The U.S. Department of Veterans Affairs Office of Research and Development provided support for this study.

*
7. Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells

This study analyzed the complex functional properties of cardiomyocytes (heart muscle cells) derived from maGSCs in vitro and the behavior of undifferentiated maGSCs in normal hearts of mice in vivo after transplantation. The authors conclude that maGSCs provide a new source of distinct types of cardiomyocytes for basic research/potential therapeutic application.

Source: Circulation Research, June 8, 2007; Circ Res. 07 Jun 8;100(11):1615-25; ahajournals/.

Funding: A grant from the Georg-August-University of GoВЁttingen supported this study.

*
8. HORIZONS: Harmonizing Outcomes with RevascularIZatiON and Stents

This large study examined the safety and effectiveness of anticoagulation medications and drug-eluting stents in patients experiencing a STEMI heart attack, in which the coronary artery is completely blocked, without significantly increasing the rate of death or recurrent heart attacks among these patients.

Source: Late-breaking trial at the Transcatheter Cardiovascular Therapeutics TCT 2007; tct2007/.

Funding: The Cardiovascular Research Foundation supported this study.

*
9. Effectiveness and safety of drug-eluting stents in Ontario

This large Canadian study found that drug-eluting stents are effective in reducing the need for target-vessel coronary artery bypass in patients at the highest risk for re-narrowing of previously blocked arteries, without a significantly increased rate of death or heart attack.

Source: New England Journal of Medicine, Oct. 7, 2007; N Eng J Med 2007; 14;357:1393-1402; nejm/.

Funding: The Ontario Ministry of Health and Long-Term Care to the Program for Assessment of Technology in Health, the CCN of Ontario and the Institute for Clinical Evaluative Sciences supported this study in part.

*
10. Underdiagnosis of Hypertension in Children and Adolescents

This study of more than 14,000 children found that hypertension and prehypertension were often undiagnosed in the pediatric population. Patient age, height, obesity-related diagnoses, and magnitude and frequency of abnormal blood pressure readings all increased the odds of hypertension.

Source: Journal of the American Medical Association, Aug. 22, 2007; JAMA 2007; 298(8):874 — 879; jama/.

Funding: This research did not receive funding support.

###

Statements and conclusions of study authors are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.

Source: Cathy Lewis

American Heart Association

New West Nile And Japanese Encephalitis Vaccines Produced

University of Texas Medical Branch at Galveston researchers have developed new vaccines to protect against West Nile and Japanese encephalitis viruses. The investigators created the vaccines using an innovative technique that they believe could also enable the development of new vaccines against other diseases, such as yellow fever and dengue fever, which are caused by similar viruses.

The scientists showed that the vaccines successfully protected laboratory mice and hamsters against the viruses, which can cause fatal brain inflammation in humans. They reported their findings in back-to-back papers published in the current issue of the journal Vaccine.

“These vaccines were created using a system that we think is applicable to producing vaccines that can protect against a wide range of diseases caused by the flaviviruses, an important family of viruses that afflict populations throughout the world,” said UTMB pathology professor Peter Mason, senior author of the Vaccine papers. “Flaviviruses cause tremendous human suffering, but we still only have vaccines for a few of them.”

Currently approved flavivirus vaccines are either “live-attenuated virus” vaccines, which contain weakened but still genetically intact versions of the target virus, or “inactivated-virus” vaccines, which contain viruses that have been chemically neutralized. In each case, the viral material stimulates the immune system to block the progress of any future infection by the virus in question.

The new vaccines – based on a concept devised by Mason and UTMB microbiology and immunology associate professor Ilya Frolov – are known as “single-cycle” or “pseudoinfectious” vaccines, and contain flaviviruses that have been genetically modified so that each virus can only infect a single cell. Unable to spread from cell to cell and create disease, these crippled viruses nonetheless continue to copy themselves within the cells they infect, thus producing the viral proteins needed to induce immune protection.

“With these vaccines, we mimic a viral infection and get amplification of the antigens that are important for stimulating an immune response without amplification of the virus,” Mason said.

To make the West Nile vaccine, the researchers deleted the piece of the West Nile virus genome that codes for a “capsid” (or “C”) protein, a part of the virus particle that encloses the genetic material of the virus and is essential to its ability to move between cells. They then introduced this truncated RNA into cells specially designed to produce high concentrations of the C protein. The result: large numbers of virus particles that had capsids but lacked the ability to pass the C gene on to their progeny.

“A vaccine virus particle grown in the C-protein expressing cells can only infect one cell in a vaccinated individual,” Mason said. “Once it gets into that cell, in order to make a new particle, it needs the C protein – and cells in the vaccinated host do not have the gene to make the C protein. But it can still make all the immunogenic proteins that the virus normally makes, and it can still generate strong immunity.”

The Japanese encephalitis vaccine was built from the West Nile vaccine, using the C-less West Nile genome but replacing the genes for two key immunogenic proteins with their Japanese encephalitis virus counterparts, a process called “chimerization.” The success of such genetic mixing and matching, Mason noted, could open the door for the creation of a wide variety of “chimerized” single-cycle flavivirus vaccines for other diseases.

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Other authors of “Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system” and “Construction and evaluation of a chimeric pseudoinfectious virus vaccine to prevent Japanese encephalitis” include UTMB graduate student Douglas G. Widman, postdoctoral fellow Tomohiro Ishikawa, associate professor Nigel Bourne and research associate Rafik Fayzulin, as well as Eiji Konishi of the Kobe University School of Medicine, Kobe, Japan. This research was supported by the NIAID through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases; Widman is supported by a fellowship from the James W. McLaughlin Endowment.

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Source: Jim Kelly

University of Texas Medical Branch at Galveston