Screening NCAA Athletes for Sudden Cardiac Death Risk

A new NCAA-funded research study supports the addition of electrocardiogram (ECG) screening to the standardized pre-participation exams for athletes to better identify cardiac abnormalities that lead to sudden cardiac death (SCD) -- the leading cause of death in athletes during sport.

                Jonathan Drezner, MD, President of the American Medical Society for Sports Medicine (AMSSM), along with a team of researchers from the University of Washington, will present their results from a recent study that was commissioned by the NCAA, entitled, "Electrocardiographic Screening in NCAA Athletes: A Multicenter Feasibility Trial in Division I Programs" this Friday at the AMSSM 22nd Annual Meeting in San Diego, Calif.

                Their prospective, multicenter trial screened 2,471 male and female athletes from 14 NCAA Division I universities. In order to be eligible for the trial, athletes could not have received an ECG screening in the past. A total of seven (0.28%) athletes were diagnosed with serious cardiac disorders, all of which had abnormal ECGs and only two of which had an abnormal history or physical exam. Notably, 4 athletes were upperclassmen who underwent prior screening by history and physical exam alone but were not identified as having a disorder at risk for SCD.

                Currently, ECG screening is not a required component of physical exams for NCAA athletes; however, according to NCAA estimates, nearly a dozen college student-athletes in the US suffer sudden cardiac arrest each year.

                Results support that ECG screening in NCAA athletes is feasible, has a low false-positive rate, and provides superior accuracy compared to a standardized history and physical exam to detect athletes with potentially dangerous cardiovascular conditions. This study also applied new international consensus standards for ECG interpretation -- an important component that minimized false-positive results.

                Dr. Drezner is a Professor in the Department of Family Medicine at the University of Washington, and Associate Director of the Sports Medicine Fellowship. Additionally he serves as team physician for the University of Washington and the Seattle Seahawks.

Tomado de sciencedaily.com

C-Peptide Levels Linked to Death and Heart Disease in Nondiabetic Adults

                High blood levels of the serum C-peptide are linked to heart disease and death in people without diabetes, according to a large study published in CMAJ (Canadian Medical Association Journal).

Researchers looked at data from the Third Nutrition and Health Examination Survey (NHANES III) and the NHANES III Linked Mortality File to determine the link between C-peptide levels and death from all causes as well as from heart disease. They looked at mortality data on 5902 adults aged 40 years or older representative of the US population. People with high serum C-peptide levels (higher than 1.018 nmol/L) had a 1.8- to 3.2-fold increased risk of death from all causes as well as cardiovascular disease-specific death compared with people with low C-peptide levels (lower than 0.440 nmol/L). The risk increased as C-peptide levels increased.

"We found a significant association between serum C-peptide levels and risk of all-cause, cardiovascular-related disease and coronary artery-related mortality among adults without diabetes," writes Dr. Kyoung-bok Min, Department of Occupational and Environmental Medicine, Ajou University School of Medicine, Suwon, Republic of Korea, with coauthor.

The study authors found that C-peptide levels were better at predicting mortality than other measures such as glycated hemoglobin and fasting blood glucose. Although the reason for the increased risk of death has not been determined, the authors suggest it may be because of the relationship between C-peptide levels and risk factors for atherogenic vascular issues.

"Our findings support the potential relevance of serum C-peptide as a predictor of adverse health outcomes and indicate that elevated C-peptide levels may be an important predictive marker of an increased risk of death," they conclude.

Tomado de: sciencedaily.com

Blockade of Pathogen's Metabolism

In the search for new antibiotics, researchers are taking an unusual approach: They are developing peptides, short chains of protein building blocks that effectively inhibit a key enzyme of bacterial metabolism. Now, scientists at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken, a branch of the Helmholtz Center for Infection Research (HZI), have published their findings and the implications for potential medical application in the scientific journal ACS Chemical Biology.

The road from gene to protein has an important stop along the way: ribonucleic acid, or RNA. This molecule is essentially a "negative copy" of DNA, the cell's hereditary material, and serves as a blueprint for the cell to make proteins, the basic building blocks of life. This "template" is assembled by the enzyme RNA polymerase, whose job it is to read off the information that is stored within the DNA molecule.

Bacterial RNA polymerase consists of several subunits. The core enzyme has to first bind a certain protein molecule called "sigma factor" which essentially allows the enzyme to begin production of the RNA molecule. The sigma factor locates the starting point of the gene to be copied -- as soon as its job is done, it once again detaches from the enzyme complex. The next time, the sigma factor and the core enzyme have to bind to each other again. If this is no longer possible, new RNA cannot be synthesized and no more proteins will be made by the cell. Cellular processes come to a complete standstill, and the bacterium dies.

Which is exactly the reason why the point of contact between the sigma factor and the core enzyme represents a potential target for new therapies against bacterial infections. Another feature makes this a particularly attractive target: "Sigma factors are unique to bacteria and are not found in mammalian cells," explains Kristina Hüsecken, Ph.D. student at the HIPS and the publication's first author. "This way, we are able to specifically target the bacteria without putting the body's own cells at risk." Which also means potential side effects are not to be expected.

The drug researchers from Saarbrücken have looked at a range of peptides, short chains of amino acids, capable of inhibiting the polymerase. Their structure corresponds to areas from the binding site of one of the enzyme parts: A perfect fit, the peptides dock either to the core enzyme or to the sigma factor, specifically at the exact location where the counterpart would normally attach to. This way, the components are prevented from combining to form a functional enzyme since the binding site is already occupied. Of the 16 total peptides the researchers examined, one in particular proved especially effective. The peptide called P07 was able to show in further tests that it actually does prevent transcription of DNA to RNA in bacterial cells by interfering with the interaction between sigma and core enzyme.

A number of current antibiotics target bacterial RNA polymerase, among them rifampicin, which was first introduced in the late 1960s. Yet these classic drugs are quickly losing their efficacy, as germs are evolving resistance to them. "Since we're looking at a new mode of action, it won't come to cross resistance, which is a much-feared issue with new antibiotics," says Dr. Jörg Haupenthal, the study's principal investigator. This could be the case with any new substance whose mode of action is similar to that of an antibiotic the bacteria have already evolved resistance to.

Whether or not P07 will be developed into a market-ready drug is something Haupenthal and his colleagues cannot predict. "Even though our research points the way to new and effective antibiotics, actually developing them into full-blown drugs for clinical use requires much additional research," says Haupenthal. As such, the researchers are working at optimizing P07 while also looking for other molecules capable of binding to the same spot on the polymerase enzyme.

Tomado de sciencedaily.com

Old Biomarker May Have New Role in Lung Ca

Bilirubin, which is considered a useful liver function marker, may also point to smokers at increased risk for lung cancer.

In a large Taiwanese prospective cohort, male smokers with bilirubin in the lowest quartile lowest had a 69% higher risk for developing lung cancer, and a 76% higher rate of lung cancer mortality, compared with male smokers who had the highest bilirubin levels, said Xifeng Wu, MD, of the University of Texas MD Anderson Cancer Center in Houston.

In men who had never smoked, bilirubin levels had no significant effect on health outcomes.

The research showed that serum bilirubin is a potential biomarker for lung cancer risk prediction, Wu told MedPage Today at the annual meeting of the American Association for Cancer Research.

"It was kind of a surprise and very interesting," Wu said. "The biomarker was identified from metabolic profiling and validated by the large, cohort study."

In the Taiwanese cohort of 435,985 individuals, the incidence rate of lung cancer in men with bilirubin levels of 0.68 mg/dL or less was 7.02 per 10,000 person-years irrespective of smoking history. This compared with a rate of 3.73 per 10,000 person-years in men whose bilirubin levels were 1.12 mg/dL or more, again irrespective of smoking history.

Wu said this translated into a 51% increase in the risk for developing lung cancer for low-bilirubin patients.

Also, the lung-cancer specific mortality rate in men with low bilirubin was 4.84 per 10,000 person-years compared with 2.46 per 10,000 person-years in men with high bilirubin.

When only male smokers were analyzed the associations were starker -- a 76% increase in lung cancer mortality.

Wu said she first conducted global, unbiased metabolomic profiling in serum samples from 20 healthy controls, 20 patients in early-stage lung cancer, and 20 patients in late-stage lung cancer. Matching for age and gender, Wu selected three differentially expressed metabolites for validation in two case-control populations. Bilirubin emerged and was validated by the large Taiwanese prospective cohort.

Wu said the study focused on male smokers and was limited by an insufficient amount of female smokers from which to draw conclusions.

But the research does point to the potential benefit of using biomarkers in cancer research, she said.

"We need to identify additional biomarkers, including metabolomic biomarkers," Wu said.

"It's a very large study and brings up interesting findings that to my knowledge haven't been reported before," said Lecia Sequist, MD, of Massachusetts General Hospital in Boston. "This will generate a lot of interesting future research in biologic relations between bilirubin and lung cancer."

Tomado de  medpagetoday.com

Ordinary Skin Cells Morphed into Functional Brain Cells

Scientists at CWRU School of Medicine Discover New Technique that Holds Promise for the Treatment of Multiple Sclerosis and Cerebral Palsy

Newswise — Researchers at Case Western Reserve School of Medicine have discovered a technique that directly converts skin cells to the type of brain cells destroyed in patients with multiple sclerosis, cerebral palsy and other so-called myelin disorders.

This discovery appears today in the journal Nature Biotechnology.

     This breakthrough now enables “on demand” production of myelinating cells, which provide a vital sheath of insulation that protects neurons and enables the delivery of brain impulses to the rest of the body. In patients with multiple sclerosis (MS), cerebral palsy (CP), and rare genetic disorders called leukodystrophies, myelinating cells are destroyed and cannot be replaced.

The new technique involves directly converting fibroblasts - an abundant structural cell present in the skin and most organs - into oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain.

     “Its ‘cellular alchemy,’” explained Paul Tesar, PhD, assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine and senior author of the study. “We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy.”

     In a process termed “cellular reprogramming,” researchers manipulated the levels of three naturally occurring proteins to induce fibroblast cells to become precursors to oligodendrocytes (called oligodendrocyte progenitor cells, or OPCs).

     Tesar’s team, led by Case Western Reserve researchers and co-first authors Fadi Najm and Angela Lager, rapidly generated billions of these induced OPCs (called iOPCs). Even more important, they showed that iOPCs could regenerate new myelin coatings around nerves after being transplanted to mice—a result that offers hope the technique might be used to treat human myelin disorders.

When oligodendrocytes are damaged or become dysfunctional in myelinating diseases, the insulating myelin coating that normally coats nerves is lost. A cure requires the myelin coating to be regenerated by replacement oligodendrocytes.

Until now, OPCs and oligodendrocytes could only be obtained from fetal tissue or pluripotent stem cells. These techniques have been valuable, but with limitations.

     “The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes,” explained co-author and myelin expert Robert Miller, PhD, professor of neurosciences at the Case Western Reserve School of Medicine and the university’s vice president for research. “The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells.”

This initial study used mouse cells. The critical next step is to demonstrate feasibility and safety using human cells in a lab setting. If successful, the technique could have widespread therapeutic application to human myelin disorders. 

     “The progression of stem cell biology is providing opportunities for clinical translation that a decade ago would not have been possible,” said Stanton Gerson, MD, professor of Medicine-Hematology/Oncology at the School of Medicine and director of the National Center for Regenerative Medicine and the UH Case Medical Center Seidman Cancer Center. “It is a real breakthrough.”

Tomado de newswise.com

New Protein Target for Controlling Diabetes

     Researchers at the University of California, San Diego School of Medicine have identified a previously unknown biological mechanism involved in the regulation of pancreatic islet beta cells, whose role is to produce and release insulin. The discovery suggests a new therapeutic target for treating dysfunctional beta cells and type 2 diabetes, a disease affecting more than 25 million Americans.

     Writing in the April 11, 2013 issue ofCell, Jerrold M. Olefsky, MD, associate dean for scientific affairs and distinguished professor of medicine, and colleagues say a transmembrane binding protein called fractalkine, which typically mediates cell-to-cell adhesion though its receptor, CX3CR1, can also be released from cells to circulate in the blood and stimulate insulin secretion.

     "Our discovery of fractalkine's role in beta cells is novel and has never been talked about in prior literature," said Olefsky. More importantly, the research highlights fractalkine's apparently vital role in normal, healthy beta cell function. In mouse models and in cultured human islets, the researchers found administering the protein stimulated insulin secretion and improved glucose tolerance, both key factors in diabetes. In contrast, fractalkine had no effect in mice or islets when the fractalkine receptor was deleted.

     "Whether or not decreased fractalkine or impaired fractalkine signaling are causes of decreased beta cell function in diabetes is unknown," said Olefsky. "What we do know, without doubt, is that administration of fractalkine improves or restores insulin secretion in all of the mouse models we have examined, as well as in human islet cells."

      Olefsky said fractalkine or a protein analog could prove "a potential treatment to improve insulin secretion in type 2 diabetic patients. It might also improve beta cell function or beta cell health, beyond simply increasing insulin secretion, since fractalkine prevents beta cell apoptosis (cell death) and promotes the beta cell differentiation program.

"If successfully developed, this could be an important new complement to the therapeutic arsenal we use in type 2 diabetes," Olefsky continued. "It is not likely to 'cure' diabetes, but it would certainly do a good job at providing glycemic control."

Tomado de sciencedaily.com

BNP screening effectively targets heart failure prevention

     Targeting a comprehensive cardiac-risk reduction program to adults with elevated natriuretic peptide significantly cut the rate of new left ventricular dysfunction, heart failure, and other cardiovascular events in a randomized trial with more than 1,300 patients.

     "I think it was the structure of the intervention, the cohesion of care, rather than a specific intervention" that improved clinical outcomes, Dr. Kenneth M. McDonald said at the annual meeting of the American College of Cardiology. "Undoubtedly, a patient’s knowledge [of a high B-type natriuretic peptide level] improved their adherence to therapy." He and his associates ran the study at 39 primary care practices around Dublin that worked in collaboration with the cardiology department at St. Vincent’s University Hospital in Dublin.

     The primary care physicians looked for patients at least 40 years old with at least one identified cardiovascular risk factor whose B-type natriuretic peptide (BNP) level rose above 50 pg/mL on an annual screening test. They referred these patients to St. Vincent’s for an intensified testing and management program similar to "the disease management structure we’ve used for several years for patients with heart failure," said Dr. McDonald, a professor of cardiology at St. Vincent’s and director of the heart failure unit. The program included a cardiology review and regular follow-up, echocardiography with Doppler and other cardiovascular investigations as needed, and nurse coaching.

     "Routine BNP screening is not recommended in current guidelines. Perhaps this finding is the first step to get guidelines committees to address the use of BNP for screening," commented Dr. Sanjay Kaul, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute at Cedars Sinai Medical Center in Los Angeles.

     Among the 1,374 patients enrolled in the STOP-HF (Screening to Prevent Heart Failure) trial, annual BNP measurement found 498 (36%) with a BNP level that rose above 50 pg/mL in at least one annual test. This included 235 patients randomized to the control arm and 263 randomized to the intervention group. The overall age of patients in the study averaged 65 years, but the age of those with elevated BNP averaged closer to 70 years.

     During average follow-up of just over 4 years, patients referred to the cardiology program had 25 cases (10%) of heart failure or asymptomatic left ventricular dysfunction, compared with 44 cases (19%) in the control arm, a 54% odds ratio reduction that was statistically significant for the study’s primary endpoint. For the entire study group of 1,374 randomized patients, participation in the group eligible for referred care cut the primary endpoint by a relative 41%, compared with the controls, a statistically significant difference.

     A secondary efficacy analysis that tallied the combined rate of incident heart failure, arrhythmia, myocardial infarction, unstable angina, cerebrovascular events, peripheral thrombosis, or pulmonary embolism found 51 events (7%) in the entire intervention group compared with 71 events (10%) in the control group, a 46% odds rate reduction that was statistically significant.

      A study limitation was the large percentage of patients in both arms either lost to follow-up, 10%; or who withdrew their consent to participate, another 16%. "It challenges interpretation of the results," commented Dr. Kaul.

But Dr. McDonald and his associates were convinced by their findings.

"We believe the results are conclusive enough to roll this out as a clinical program," he said in an interview. "We are now extending this to another region of Ireland, and we will try to get this disseminated nationally."

He also foresees additional refinements to the program, possibly identifying other risk markers that can compliment BNP and further focus intervention.

"We have shown benefit, but a question is the cost of getting that benefit. BNP is clearly a step up from where we were, but that doesn’t mean we are as good as we could make it."

Tomado de: ecardiologynews.com

Oxygen treatment may not help foot ulcers

Despite past clinical trials demonstrating that exposure to pure oxygen can help stubborn wounds heal, a large new study of diabetes patients with severe foot ulcers finds no benefit from oxygen treatments and possibly some harm.

Researchers following more than 6,000 diabetes patients receiving treatment for deep foot wounds found that patients who got oxygen-chamber treatments along with standard wound care were no more likely to heal and more than twice as likely to undergo amputations as those getting standard care alone.

The results, published in the journal Diabetes Care, surprised the study team from the University of Pennsylvania, not least because they defy so much previous research.

"We really thought we would see a replication of what occurred in the randomized trials. The data demonstrates that didn't come to pass," said Dr. Stephen Thom, a professor at the Perelman School of Medicine in Philadelphia who worked on the study.

For more than 20 years, people with serious open wounds or burns have been put into pressurized chambers or rooms that expose them to pure oxygen, in the belief that it helps to promote tissue growth and speed healing.

Because of nerve and blood vessel damage, people with diabetes are at risk of persistent ulcers forming on their toes and heels - wounds that can become infected and even lead to gangrene and amputation. Oxygen treatments are sometimes added to standard care of diabetic foot wounds to enhance healing.

For the new study, researchers wanted to see whether the oxygen therapy was making a difference in real-world settings.

They analyzed data on 6,259 diabetes patients treated for foot ulcers at wound care centers around the U.S. between November 2005 and May 2011.

Of those patients, only 793 ended up having the oxygen therapy on top of standard care. Their sessions lasted from 45 minutes to two hours in the pressurized chambers, and were done once or twice per day over four to five times per week.

Thom told Reuters Health that such treatments typically cost between $300 and $600 per session.

After 16 weeks, about 43 percent of oxygen therapy patients had fully healed wounds, compared to about 50 percent of patients who did not use oxygen therapy. And about 7 percent of oxygen therapy patients had an amputation, compared to just 2 percent of those who did not get oxygen treatments.

"It does not only say it's not equal, it says it may be worse. You're seeing a higher amputation rate and a longer healing of a foot wound," said Dr. Nicholas Morrissey, a vascular surgeon at New York-Presbyterian Hospital.

But Morrissey, who was not involved in the new research, also noted that all the previous studies and trials to have looked at oxygen therapy have had limitations, as did this one.

The authors point out in their report as well that further study is needed to better understand the current results and the effects of oxygen treatments.

For example, the team attempted to adjust for issues that might have influenced the outcomes, such as whether patients with worse wounds or additional illnesses might have been more likely to get oxygen treatments. But the nature of the study makes it impossible to know for sure, they write.

"It certainly could be that they're picking people who are more severe (for oxygen treatment), but we tried to compensate for that," the study's lead author Dr. David Margolis, also from the Perelman School of Medicine, told Reuters Health.

"It's like many things in medicine, it's just one other study and you have to look at the totality of the information available," Margolis cautioned.

Morrissey said that until a definitive study is done, patients shouldn't be afraid or concerned that they're going to have an amputation after oxygen therapy.

"As a physician who takes care of these wounds all the time, I wouldn't tell patients to be concerned… I would not take that home from this paper," he said.

SOURCE: bit.ly/W7ZXTZ Diabetes Care, online February 19, 2013.

Tomado de Reuters.com