Scientists at Queen’s University Belfast have discovered that proteins in frog skins could be used to treat cancer, diabetes, stroke and transplant patients by regulating the growth of blood vessels.

The researchers identified two proteins, or “peptides”, which can be used in a controlled and targeted way to regulate “angiogenesis.”  The discovery holds the potential to develop new treatments for more than seventy major diseases and conditions that affect over a billion people worldwide.

Scientists captured the frogs and extracted the secretions before releasing them back into the wild. 

Chris Shaw, a professor at Queen’s School of Pharmacy who led the research, said in a statement: “The proteins that we have discovered have the ability to either stimulate or inhibit the growth of blood vessels. By ‘switching off’ angiogenesis and inhibiting blood vessel growth, a protein from the Waxy Monkey Frog has the potential to kill cancer tumors.”

Shaw said most cancer tumors can only grow to a certain size before they need blood vessels to grow into the tumor to supply it with oxygen and nutrients.

Stopping the blood vessels from growing will cause the tumor to be less likely to spread, and could eventually kill it.

This effect has the potential to transform cancer from a terminal illness into a chronic condition.

“On the other hand, a protein from the Giant Firebellied Toad has been found to ‘switch on’ angiogenesis and stimulate blood vessel growth. This has the potential to treat an array of diseases and conditions that require blood vessels to repair quickly, such as wound healing, organ transplants, diabetic ulcers, and damage caused by strokes or heart conditions,” Shaw said in a statement.

He said “Because of its huge potential, angiogenesis has been a prime target for drugs development research over the past forty years. But despite an investment of around $4-5 billion by scientists and drugs companies around the world, they have yet to develop a drug that can effectively target, control and regulate the growth of blood vessels.

“The aim of our work at Queen’s is to unlock the potential of the natural world ““ in this case the secretions found on frog and toad skins – to alleviate human suffering. We are absolutely convinced that the natural world holds the solutions to many of our problems, we just need to pose the right questions to find them.

“It would be a great shame to have something in nature that is potentially the wonder drug to treat cancer and not aim to do everything in our power to make it work.”

The researchers will receive the Commendation in the Cardiovascular Innovation Award at the Medical Future Innovation Awards in London Tuesday night. 

The award is one of Europe’s most prestigious healthcare and business awards.

Queen’s Vice-Chancellor Professor Peter Gregson said in a statement, congratulating the team on their research: “This award is not only an honor for Professor Shaw and his team, it is recognition of the world-class research taking place at Queen’s School of Pharmacy, and the life-changing potential of the University’s work in drug discovery.”

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Image Caption: Waxy Tree Frog Phyllomedusa sauvagii at the Cotswold Wildlife Park, Burford, Oxfordshire, England. Credit: Adrian Pingstone/Wikipedia  

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On the Net:

• Queen’s University Belfast

One in three women will be faced at least once in her life with cystitis, for some the start of a constantly recurring infection. Cystitis is caused by Escherichia coli bacteria which fasten on to the wall of the bladder by means of thread-like structures (pili). Han Remaut of the VIB Department for Structural Biology Brussels, Vrije Universiteit Brussel reveals for the first time the complex interactions which lead to the formation of these pili. This knowledge can be used to develop new antibiotics to treat infections of the urinary tract.

Cystitis

Around 80% of infections of the urinary tract are caused by the Escherichia coli bacteria, gram-negative rod-like bacteria. Although these bacteria form part of normal intestinal flora, virulent types can penetrate the bladder via the urethra and lead to urinary tract infections. These infections occur more often in women than in men and account for a large number of hospital-acquired infections, especially in the case of catheterized patients. Treatment consists of using existing antibiotics. However, the current generation of antibiotics is losing its power to fight these bacteria. Especially problematic are recurrent infections. There is an urgent need for new antibiotics.

Bacteria adhere to the cells of the urinary bladder

Bacteria can adhere to a surface due to their hair-like structures, known as pili or fimbriae. In the case of uropathogenic E. coli, type 1 pili occur which consist of four different sub-entities. The biosynthesis (formation) of these pili takes place through a conserved mechanism (the chaperone/usher biosynthesis route). As type 1 pili are responsible for the uropathogenic E. coli adhering to the host cells, these are promising targets for new antibacterials.

Structural biological techniques to investigate pili formation

Han Remaut, together with colleagues working for the Institute of Structural and Molecular Biology, University of London, is investigating the mechanism responsible for the biosynthesis of these pili. For this purpose, they are using X-ray diffraction – the standard technique for determining the structure of proteins. Detailed knowledge about the structure of proteins is necessary to gain an insight into how they function.

Han Remaut and colleagues were the first to successfully image the assembly complex leading to pili biosynthesis. Furthermore, this is also the first snapshot of a protein transporter in action.

New antibiotics for the treatment of infections of the urinary tract

This detailed knowledge about the biosynthesis of type 1 pili from E. coli can form the basis for the development of medicines which block the formation of the pili. If bacteria can no longer cling to the epithelial cells of the bladder, they will no longer be able to cause an infection. The mechanism responsible for E.coli attaching to the bladder is also used by other bacteria. As a result, this research can also contribute to the fight against other infectious diseases such as food poisoning or traveler’s diarrhea.

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On the Net:

• VIB (the Flanders Institute for Biotechnology)

Two promising new treatments to aid people with autism have shown effectiveness in pilot studies conducted by an Arizona State University professor and private researchers.

Several studies indicate that children with autism often have abnormalities in critical biochemical functions that help maintain health ““ specifically methylation, glutathione, and mitochondrial functions.

Methylation turns proteins in the body on and off ““ including DNA and RNA ““ a function that controls gene activity.

Glutathione, a primary antioxidant, provides a defense against toxic metals in the body. Mitochondria are essentially the “factories” inside body cells that produce energy.

The research team has been developing therapies aimed at restoring or improving these functions in people with autism experiencing abnormalities.

The complete study is published in the medical journal Autism Insights.

The team includes:

“¢ James Adams, a professor in the School for Engineering of Matter, Transport and Energy, one of ASU’s Ira A. Fulton Schools of Engineering

“¢ Stuart Freedenfeld, physician and medical director with Stockton Family Practice, in Stockton, N.J.

“¢ Tapan Audhya, a biochemist with the Health Diagnostics and Research Institute, in South Amboy, N.J.

“¢ Kim Hamada, a registered nurse with Stockton Family Practice.

A common feature of the abnormalities the researchers are studying is that they are affected directly or indirectly by levels of specific substances produced by the body ““ ribose and nicotinamide adenine dinucleotide, or NADH.

Use of ribose and NADH supplements have been reported to boost levels of adenosine-5′-triphosphate, or ATP ““ a primary fuel source for the body and the brain. The supplements have also been shown to be helpful in treating chronic fatigue.

The research team explored use of ribose and NADH supplements as treatments for autism in two parallel studies using ribose and NADH.

One study investigated the effect of supplementation with NADH, an important co-factor for many enzymatic reactions in the body.

Another study investigated the effect of supplementation with ribose, a special sugar made by the body from glucose.

The studies found use of ribose and NADH supplements had similar effects, boosting levels of methylation, glutathione and ATP after only two weeks of therapy.

Levels of ribose and NADH also improved substantially, without adverse effects. After just two weeks of therapy, one child in each group was reported to have some improvement in energy level.

The biochemistry of both NADH and ribose is well-established, as well as how both affect production of ATP, glutathione and methylation. Details are provided in the article in Autism Insights.

Adams points out that both treatments use products that are available as over-the-counter nutritional supplements.

Larger and more formal studies are needed to confirm the benefits of ribose and NADH supplements, Freedenfeld says.

But “these therapies appear to be safe and effective supportive therapies for restoring methylation, glutathione and ATP to near-normal levels in the body, and are likely to help children with autism who experience problems maintaining normal functions,” he says.

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On the Net:

• ASU

The gold standard long-term glucose monitoring test for patients with diabetes proved to be of limited value in dialysis patients, according to a new study at Wake Forest Baptist Medical Center.

The study appears online in the Clinical Journal of the American Society of Nephrology and is scheduled for the July print issue.

Blood sugar monitoring is a vital part of diabetes management. Patients and physicians rely on the hemoglobin A1c (HbA1c) test to measure an individual’s average blood sugar level over the prior three months. It is the most commonly used long-term blood sugar test, and is widely trusted in the medical community.

While the American Diabetes Association has deemed the HbA1c test an effective tool for diagnosing diabetes, kidney doctors recently determined that the HbA1c is not as useful for managing patients with diabetes and advanced kidney failure. Another test, the glycated albumin or GA assay, appears to be far more effective in this setting.

“Many organs don’t function properly in severe kidney failure,” explained Barry I. Freedman, M.D., John H. Felts III Professor and lead investigator. “For example, most dialysis patients have anemia with fewer red blood cells than they should, which has a dramatic impact on the accuracy of the HbA1c reading.”

Hemoglobin inside red blood cells carries oxygen in the body. Blood sugar chemically interacts with the hemoglobin to identify a value for HbA1c. But HbA1c results are only accurate when red cells have a normal lifespan. Dialysis patients have shorter red cell survival, reducing the time that sugar in the bloodstream has to interact with hemoglobin, and causing lower HbA1c values.

“Doctors long thought the HbA1c predicted outcomes in diabetes,” Freedman said. “This test is not predictive of outcomes in diabetes patients with kidney disease on dialysis. Dialysis patients and physicians get a false sense of security because their lower HbA1c actually relates to shorter red cell survival, yet suggests diabetes control is better than it really is.”

Nearly 500,000 people are on dialysis in the Unites States and diabetes is the cause of kidney failure in nearly 50 percent of them. Diabetes is the most common cause of kidney failure worldwide and is associated with high mortality rates ““ more than 20 percent of dialysis patients die each year. As such, there is an urgent need for accurate blood sugar testing in diabetic dialysis patients.

Freedman and colleagues evaluated 444 patients with diabetes undergoing dialysis. Patients continued their normal treatment and HbA1c monitoring, but also agreed to have a GA test every three months for an average of more than 2.3 years.

The GA test, developed by Tokyo-based Asahi Kasei Pharma Corporation, measures blood sugars over the past 17 days, as opposed to the longer time frame for HbA1c. In situations where rapid changes occur in blood sugar, the GA gives a more accurate picture of diabetes control. The GA test used in this study is available in Japan, China and South Korea, but is not yet FDA approved in the United States.

Wake Forest Baptist researchers compared the patients’ HbA1c and GA test results, assessing their ability to predict hospitalizations and survival. They found that the HbA1c failed to predict these important medical outcomes. In contrast, the GA was a strong predictor of patient survival and hospitalizations.

“This is the first study showing that a blood sugar test predicts risk of death in diabetic dialysis patients, as well as risk of hospitalization,” Freedman said. “This test provides the missing link that will allow dialysis patients and physicians to accurately gauge risk. The association is clear: high GA readings predict higher risk.”

Freedman suggests physicians not rely on the HbA1c in dialysis patients, instead suggesting that blood glucose levels be directly monitored with multiple daily readings until the GA test is available in the states.

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On the Net:

• Wake Forest Baptist Medical Center
• Clinical Journal of the American Society of Nephrology

Is it really possible for people with perfectly normal hearing to become deaf to the world around them when they are concentrating on another subject? New research funded by the Wellcome Trust suggests it is in fact possible.
The new study, published in the journal “Attention, Perception, & Psychophysics’, suggests that focusing heavily on a task results in the experience of deafness to other sounds within earshot. Researchers at University College London (UCL) demonstrate this phenomenon — called “inattentional deafness” — for the first time.
“Inattentional deafness is a common everyday experience,” explains Professor Nilli Lavie from the Institute of Cognitive Neuroscience at UCL. “For example, when engrossed in a good book or even a captivating newspaper article we may fail to hear the train driver’s announcement and miss our stop, or if we’re texting whilst walking, we may fail to hear a car approaching and attempt to cross the road without looking.”
Lavie, along with one of her PhD students, James Macdonald, devised a series of experiments designed to test for inattentional deafness. More than a hundred participants were involved in the experiments. The subjects were asked to perform tasks on a computer involving a series of shapes. Tasks varied from very simple to difficult.
Participants wore headphones while carrying out the tasks being told by researchers that they were to aid their concentration levels. At some point during the tasks a tone was played unexpectedly through the headphones. At this point in the experiment, the tasks were stopped and researchers asked if the participants had heard this sound.
During the simple tasks where little concentration is needed, about 2 in ten participants missed the tone. However, when focusing on a more difficult task, about 8 in ten of the participants failed to pick up the sound.
The researchers believe that when peoples’ attention is fully taken by a purely visual task the result is limited capability in processing sounds.
It is already known that people similarly experience “inattentional blindness” when engrossed in a task that takes up all of their attentional capacity. An example of attentional blindness is the Invisible Gorilla Test, where observers engrossed in a basketball game fail to observe a man in a gorilla suit walk past.
The new research shows that being fully engrossed in difficult tasks makes us blind and deaf to other sources.
Inattentional deafness is “a common everyday experience,” Lavie told the Telegraph.
“Hearing is often thought to have evolved as an early warning system that does not depend on attention, yet our work shows that if our attention is taken elsewhere, we can be effectively deaf to the world around us,” said Lavie.
Inattentional deafness could be a real world hazard. It has been well documented that a large number of accidents have occurred due to a driver’s inattention and this new research suggests inattentional deafness is yet another contributing factor.
The researchers did not look at whether men or women were more prone to inattentional deafness.
“From my own personal experience, I suspect that men are more susceptible,” Lavie laughed. “But that’s not based on any scientific knowledge,” she noted.
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On the Net:

• Wellcome Trust
• Attention, Perception, & Psychophysics
• Institute of Cognitive Neuroscience, University College London

Caffeine reduces muscle activity in the Fallopian tubes that carry eggs from a woman’s ovaries to her womb. “Our experiments were conducted in mice, but this finding goes a long way towards explaining why drinking caffeinated drinks can reduce a woman’s chance of becoming pregnant,” says Professor Sean Ward from the University of Nevada School of Medicine, Reno, USA. Ward’s study is published today in the British Journal of Pharmacology.

Human eggs are microscopically small, but need to travel to a woman’s womb if she is going to have a successful pregnancy. Although the process is essential for a successful pregnancy, scientists know little about how eggs move through the muscular Fallopian tubes. It was generally assumed that tiny hair-like projections, called cilia, in the lining of the tubes, waft eggs along assisted by muscle contractions in the tube walls.

By studying tubes from mice, Professor Ward and his team discovered that caffeine stops the actions of specialised pacemaker cells in the wall of the tubes. These cells coordinate tube contractions so that when they are inhibited, eggs can’t move down the tubes. In fact these muscle contractions play a bigger role than the beating cilia in moving the egg towards the womb. “This provides an intriguing explanation as to why women with high caffeine consumption often take longer to conceive than women who do not consume caffeine,” says Professor Ward.

Discovering the link between caffeine consumption and reduced fertility has benefits. “As well as potentially helping women who are finding it difficult to get pregnant, a better understanding of the way Fallopian tubes work will help doctors treat pelvic inflammation and sexually-transmitted disease more successfully,” says Professor Ward. It could also increase our understanding of what causes ectopic pregnancy, an extremely painful and potentially life-threatening situation in which embryos get stuck and start developing inside a woman’s Fallopian tube.

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On the Net:

• Wiley-Blackwell
• British Journal of Pharmacology

For guys looking to catch the eye of a female, research suggests that you don’t smile too much and show a bit of brooding. Canadian researchers have discovered that women find men less attractive if they appear happy and smiling, Reuters reports.

“Men who smile were considered fairly unattractive by women,” said Jessica Tracy, a University of British Columbia psychology professor who directed the study.

Men’s reaction to what is attractive about women is the opposite, “Women who smile are absolutely very attractive. That was by far the most attractive expression women showed,” Tracy said in an interview with Reuters reporter Allan Dowd.

The study published online in the American Psychological Association journal Emotion consisted of more than 1,000 adults that were asked to rate the sexual attractiveness of hundreds of photos of the opposite sex. These pictures showed men and women engaged in various displays of happiness, with broad smiles, pride – raised heads, puffed-out chests, and shame – lowered heads or averted eyes.

Study co-author Alec Beall, a psychology graduate student, told the Telegraph: “We explored first-impressions of sexual attraction to images of the opposite sex. “We did not ask participants if they thought these targets would make a good boyfriend or wife – we wanted their gut reactions on carnal, sexual attraction.”

Other studies suggest that what people find attractive has been shaped by centuries of evolutionary and cultural forces. Evolutionary theories suggest women may be attracted to male displays of pride because they imply status, competence and an ability to provide for a partner and offspring, The Telegraph reports.

Beall added that expressions of pride also exaggerate typically masculine physical features, such as upper body size and muscularity.

The researchers admit they are not sure why men and women reacted differently to smiles. In a man, a big smile may make him appear too feminine or more desperate for sex. The study also adds to the notion that women are attracted to bad boys.

“Women are attracted to guys like James Dean, Edward the vampire. The guys who are flawed, but who know it and are tortured by it,” Tracy said.

A slightly downcast expression of shame is an appeasement gesture that hints at a need for sympathy. Men also found sexual attractiveness in women whose expressions and body language hinted at shame.

The researchers stressed they looked only at initial reactions of sexual attractiveness, and were not recommending men adopt a no-smile policy for a long-term relationship. “When people want a long-term relationship they take much more into account than sexual attractiveness. How nice a person is, is a big thing. So we’re not saying, don’t be a nice guy,” Tracy explained.

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On the Net:

• University of British Columbia
• Emotion

Article in Journal of Bone and Joint Surgery will be subject of educational video

When two adjacent discs in the low back wear out, become compressed and cause unmanageable pain, numbness or other symptoms, replacement with artificial discs can be a viable alternative to standard fusion surgery, based on two-year post-surgery data from a randomized, multicenter trial recently published in the Journal of Bone and Joint Surgery.

Previous studies have compared single-disc replacement with fusion but this is believed the first to evaluate the two forms of treatment for two contiguous discs, said Rick B. Delamarter, MD, vice chair for Spine Services in the Department of Surgery and co-medical director of the Spine Center at Cedars-Sinai Medical Center. He is the article’s first author.

As part of the approval process for a specific artificial disc (the ProDisc-L), the study was designed to meet Food and Drug Administration criteria comparing overall results from a disc replacement patient group with those of a fusion group. Those comparisons found the two therapies comparable in terms of outcomes deemed favorable, but Delamarter said individual patient outcomes suggest the disc replacement operation may have advantages.

“Overall, 24 months after surgery, patients in both groups had less pain and were able to reduce their use of medication, but the percentages were higher in the disc replacement group. Seventy-three percent of disc replacement patients met the study’s pain improvement criteria, compared with less than 60 percent of the fusion patients. Of these, only 19 percent in the disc replacement group continued to need narcotics for pain, compared with 40 percent in the fusion group. Also, more disc replacement patients said they were satisfied with their outcomes and would choose to have the surgery again,” Delamarter said.

The article reported that disc replacement operations were quicker and resulted in less blood loss, hospital stays were shorter and patients experienced more rapid improvement.

Discs act as cushions between the bones (vertebrae) of the spine. When healthy, they have enough “give” to allow the back to be flexible but they are firm enough to provide stability. With age or injury, they can lose their pliability and density. Nerves may become pinched between the bones, causing pain not just in the spine but in other parts of the body.

Fusion surgery is intended to relieve symptoms of degenerative disc disease by removing the damaged disc and replacing it with bone. Rods and screws are attached to the spine to hold the bones in place while the vertebrae grow together (fuse). Studies show these procedures often can be effective in certain situations but there can be drawbacks: fused sections of the spine can lose their flexibility, potentially impeding normal movement and putting greater stress on the surrounding discs. The adjacent discs then can be prone to injury, often requiring more fusion surgery.

Artificial discs are designed to maintain natural spine movement. They may reduce the need for follow-up surgery.

“Although our data extend two years out from surgery, fully evaluating the benefits or disadvantages of either procedure will require longer follow-up to detect adjacent-level disc degeneration and possible device wear,” said Delamarter, who joined Cedars-Sinai in 2009.

In a commentary on the article in the same journal, Andrew J. Schoenfeld, MD, of the William Beaumont Army Medical Center in El Paso, Texas, said the authors “are to be commended for an important work that contributes substantially to the growing literature regarding total disc replacement. While it has limitations, the work of Delamarter et al. should be recognized as the first prospective, randomized study on two-level total disc replacement and one that highlights short-term clinical advantages for the procedure, such as accelerated rehabilitation and enhanced pain relief.”

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On the Net:

• Cedars-Sinai Medical Center
• Journal of Bone and Joint Surgery

Pity the lowly astrocyte, the most common cell in the human nervous system.

Long considered to be little more than putty in the brain and spinal cord, the star-shaped astrocyte has found new respect among neuroscientists who have begun to recognize its many functions in the brain, not to mention its role in a range of disorders of the central nervous system.

Now, writing in the May 22 issue of the journal Nature Biotechnology, a group led by University of Wisconsin-Madison stem cell researcher Su-Chun Zhang reports it has been able to direct embryonic and induced human stem cells to become astrocytes in the lab dish.

The ability to make large, uniform batches of astrocytes, explains Zhang, opens a new avenue to more fully understanding the functional roles of the brain’s most commonplace cell, as well as its involvement in a host of central nervous system disorders ranging from headaches to dementia. What’s more, the ability to culture the cells gives researchers a powerful tool to devise new therapies and drugs for neurological disorders.

“Not a lot of attention has been paid to these cells because human astrocytes have been hard to get,” says Zhang, a researcher at UW-Madison’s Waisman Center and a professor of neuroscience in the UW-Madison School of Medicine and Public Health. “But we can make billions or trillions of them from a single stem cell.”

Although astrocytes have gotten short shrift from science compared to neurons, the large filamentous cells that process and transmit information, scientists are turning their attention to the more common cells as their roles in the brain become better understood. There are a variety of astrocyte cell types and they perform such basic housekeeping tasks as helping to regulate blood flow, soaking up excess chemicals produced by interacting neurons and controlling the blood-brain barrier, a protective filter that keeps dangerous molecules from entering the brain.

Astrocytes, some studies suggest, may even play a role in human intelligence given that their volume is much greater in the human brain than any other species of animal.

“Without the astrocyte, neurons can’t function,” Zhang notes. “Astrocytes wrap around nerve cells to protect them and keep them healthy. They participate in virtually every function or disorder of the brain.”

The ability to forge astrocytes in the lab has several potential practical outcomes, according to Zhang. They could be used as screens to identify new drugs for treating diseases of the brain, they can be used to model disease in the lab dish and, in the more distant future, it may be possible to transplant the cells to treat a variety of neurological conditions, including brain trauma, Parkinson’s disease and spinal cord injury. It is possible that astrocytes prepared for clinical use could be among the first cells transplanted to intervene in a neurological condition as the motor neurons affected by the fatal amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, are swathed in astrocytes.

“With an injury or neurological condition, neurons in the brain have to work harder, and doing so they make more neurotransmitters,” chemicals that in excess can be toxic to other cells in the brain, Zhang says.

“One idea is that it may be possible to rescue motor neurons by putting normal, healthy astrocytes in the brain,” according to Zhang. “These cells are really useful as a therapeutic target.”

The technology developed by the Wisconsin group lays a foundation to make all the different species of astrocytes. What’s more, it is possible to genetically engineer them to mimic disease so that previously inaccessible neurological conditions can be studied in the lab.

In addition to Zhang, co-authors of the new Nature Biotechnology paper include Robert Krencik, Jason Weick and Zhijian Zhang, all of UW-Madison, and Yan Liu of Fudan University Shanghai Medical School. The work was supported by the ALS Foundation, the National Institute of Neurological Disorders and Stroke, the National Multiple Sclerosis Society, the Bleser Family Foundation and the Busta Family Foundation.

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Image Caption: Astrocytes are star-shaped cells that are the most common cell in the human brain and have now been grown from embryonic and induced stem cells in the laboratory of UW-Madison neuroscientist Su-Chun Zhang. Once considered mere putty or glue in the brain, astrocytes are of growing interest to biomedical research as they appear to play key roles in many of the brain’s basic functions, as well as neurological disorders ranging from headaches to dementia. In this picture astrocyte progenitors and immature astrocytes cluster to form an “astrosphere.” The work was conducted at UW-Madison’s Waisman Center. Credit: Robert Krencik/ UW-Madison

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On the Net:

• University of Wisconsin-Madison
• Nature Biotechnology

Millions of chronic back pain sufferers could soon find relief from a new gel invented by British scientists that repairs damaged spinal discs, according to a published study in the journal Soft Matter.

At some point in their lives, at least 80 percent of people are affected by back pain, which is most frequently caused by degeneration of the intervertebral disc. It is the most common cause of job-related disability and is one of the main reasons why people miss work in the United States.

Professor Tony Freemont, Head of Research in the School of Biomedicine at the University of Manchester, and co-author on the paper, says, “Degeneration of the intervertebral disc results in chronic back pain which costs the country billions of pounds per annum and causes untold misery for sufferers and their families.”

Now scientists, after 25 years of research, have developed a biomaterial implant which could treat chronic back pain, the study says.

Microscopic sponge-like particles which inflate and gel together to repair worn-away discs may be the answer back pain sufferers are looking for.

Lead researcher Dr. Brian Saunders of the School of Materials and his team have successfully linked the microgel particles together to form injectable elastic gels that are capable of sustaining large permanent changes in shape without breaking and which have long-term durability required for an implanted device, the study says.

“Our team has made a breakthrough through innovative materials design that brings the prospect of an injectable gel for treating degeneration of the intervertebral disc a step closer,” Dr. Saunders says.

Professor Freemont adds, “We have been working for 25 years to identify methods for treating degeneration of the intervertebral disc.”

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On the Net:

• Soft Matter
• University of Manchester

Colorectal cancer patients with defects in mismatch repair–one of the body’s systems for repairing DNA damage–have lower recurrence rates and better survival rates than patients without such defects, according to a study published online May 19th in the Journal of the National Cancer Institute.

About 15% of colorectal cancers are associated with mismatch repair defects. Some defects are caused by the inherited gene mutations found in Lynch syndrome and others occur by chance, or “sporadically.” But it has never been clear whether mismatch repair defects are linked to cancer recurrence rates, time-to-recurrence and site of recurrence and whether such defects influence response to chemotherapy.

To explore these questions, Frank A. Sinicrope, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues analyzed data from more than 2,000 clinical trial patients who had been treated after surgery with chemotherapy that included 5-fluorouracil (5-FU), a standard drug used in colorectal cancer. All patients had stage II or III colon cancer.

The patients with defective mismatch repair had lower rates of tumor recurrence, longer remissions, fewer metastases, and better survival rates compared to those without the defects. Both overall survival and disease-free survival were improved.

Whether mismatch repair status influences response to 5-FU therapy has been a subject of some debate. In this study treatment with 5-FU reduced recurrence rates in stage III, regardless of mismatch repair status, but not stage II patients.

The researchers also compared the effects of 5-FU-based therapy in patients thought to have inherited mismatch repair defects versus those whose defects occurred sporadically. They suggest that 5-FU appeared to reduce recurrences only in those with inherited defects.

“In conclusion,” they write, “our data demonstrate that patients with defective mismatch repair colon cancers have a statistically significant reduction in their rates of tumor recurrence, a delayed time to recurrence, and better survival rates” than those without the defects. They note that the difference between inherited and sporadic tumors, though a preliminary finding, warrants further study.

In an accompanying editorial, Sabine Tejpar,M.D., Ph.D., of University Hospital Gasthuisberg, Leuven, Belgium, and colleagues note that the influence of mismatch repair defects on patients’ prognosis and response to 5-FU has long been a contentious issue. They say that this study, with its large number of samples, provides “valuable information about the prognostic and certainly the predictive role” of mismatch repair defects. The editorialists conclude that it will be important to validate whether patients should have their mismatch repair defects identified as hereditary or sporadic before deciding on chemotherapy with 5-FU.

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On the Net:

• Journal of the National Cancer Institute

A subset of breast cancer patients who have tumors overexpressing a protein called the human epidermal growth factor receptor 2 (HER-2 positive) may benefit from a combination of targeted treatments and may not need chemotherapy, said researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine on behalf of the Translational Breast Cancer Research Consortium in an abstract released today by the American Society of Clinical Oncology.

Dr. Jenny Chang, previously with the Smith Breast Center and now director of the Methodist Cancer Center in Houston, will present the results of this clinical study (TBCRC 006) in an oral presentation at the annual ASCO meeting in Chicago in June.

The clinical trial involved 64 women with large tumors that tested positive for HER-2 and some that were also estrogen-receptor positive. Using two drugs ““ lapatinib and trastuzumab ““ that target HER-2 in different ways, physicians were able to eradicate tumors in 38 percent of estrogen-receptor negative patients and 21 percent of estrogen receptor-positive patients, said Dr. C. Kent Osborne, director of the Smith Breast Center and a senior author of the report. Estrogen-receptor positive patients were also given an aromatase inhibitor to stop production of estrogen.

Preclinical models developed at BCM

“We have shown in preclinical models that complete blockage of the HER-2 family including HER-1, 2 and 3 with the drugs lapatinib and trastuzumab leads to eradication of HER-2 positive tumors in mice,” said Dr. Mothaffar Rimawi, medical director of the Smith Breast Center and current principal investigator on the study. “These drugs alone only partially inhibit the pathway, quickly resulting in resistance to treatment.” Rimawi developed this model in 2004 as a fellow in the laboratory of Osborne and Dr. Rachel Schiff, associate professor in the Smith Breast Center and a co-author on the paper.

“We conducted two prior clinical studies over the last ten years that show that lapatinib and trastuzumab are effective as single agents but our preclinical data suggested they would likely work better when used together,” said Chang.

The research team at Baylor College of Medicine sought to translate these findings to patients, so they initiated a multicenter clinical trial through the TBCRC.

The same response (eradication of tumors) that Rimawi and his team observed in preclinical models in the laboratory was also seen in many patients in this clinical trial, Osborne said.

Study design

The TBCRC 006 trial recruited a total of 64 patients through the Smith Breast Center (at the Baylor Clinic and Ben Taub General Hospital sites), the Vanderbilt University School of Medicine, the University of Alabama at Birmingham, the University of Chicago, and the Mayo Clinic College of Medicine.

The patients had large (average of 6 cm) HER-2 positive tumors in the breast when they were initially diagnosed. They were given a combination of lapatinib (Tykerb®) daily and trastuzumab (Herceptin®) once weekly for 12 weeks before surgery without standard chemotherapy. Lapatinib is a pill that blocks the enzyme activity of HER-2 and its close family member HER-1. Trastuzumab is an antibody administered intravenously that blocks HER-2 in a different way. Some patients’ tumors were also estrogen-receptor positive (grow in the presence of the hormone estrogen). These patients were given an aromatase inhibitor to stop production of estrogen.

“With this combination, we are able to block all of the cancer-promoting signals from the HER family, which we know is crucial for growth of this kind of breast cancer,” said Osborne, also director of the NCI-designated Dan L. Duncan Cancer Center at BCM. “Each of these drugs hits a different receptor, thereby shutting down the pathway responsible for the breast cancer’s growth.”

No patients were given chemotherapy during that 12-week period. Tumor biopsies were gathered at study entry, 2, 8 and 12 weeks (the time of surgery) to study how the drugs were working.

Study results

After 12 weeks, 38 percent of the estrogen-receptor negative, HER-2 positive patients had eradication of invasive breast cancer from the breast ““ “the type of breast cancer that can spread beyond your breast and invade healthy, surrounding tissue, and other organs,” said Rimawi.

A significant benefit was also observed in the estrogen-receptor positive group, Rimawi said. “Twenty-one percent of these patients had complete disappearance of their tumors and another 34 percent had near eradication with only small amounts of tumor left after treatment.”

“We have seen similar results in other recently reported studies using the lapatinib/trastuzumab combination, but this is the first study not to use chemotherapy,” said Osborne. “The side effects of chemotherapy can be significant and eliminating the need for chemotherapy in certain patients would represent a groundbreaking approach to treatment.”

Another strong point of this trial was the representation of minority women in the study group. Of the group, 33 percent were Hispanic and 21 percent were African-American, Rimawi said.

Next steps in research

“Our next step with this research will be to determine the optimal duration of treatment,” said Rimawi. “In an upcoming multicenter TBCRC clinical trial led by us at Baylor College of Medicine, we will compare 12 weeks with 24 weeks of treatment.” Studies are underway now to identify which patients can be safely treated without chemotherapy for this subtype of breast cancer which used to be considered difficult to treat.

For more information on enrolling in that trial, please contact Anne Pavlick at 713-798-7814 or [email protected].

This study was supported by GlaxoSmithKline and the Translational Breast Cancer Research Consortium.

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On the Net:

• BCM

With a recently announced $125,000 grant, the Houston Affiliate of Susan G. Komen for the Cure© will continue its support of physicians in the Lester and Sue Smith Breast Center at Baylor College of Medicine who provide breast cancer care to Houston’s medically underserved and uninsured at Ben Taub General Hospital.

“We are committed to our efforts at Ben Taub Hospital,” said Dr. Mothaffar Rimawi, medical director of the Smith Breast Center. “With the continued support from Komen Houston, we are able to provide the level of access to breast cancer care and prevention that all women deserve.”

Ninth year of support

This is the ninth year in a row that Komen Houston has renewed their support for Smith Breast Center physicians at Ben Taub Hospital, which is part of the Harris County Hospital District.

The Houston Affiliates’ support has enabled Ben Taub Hospital to offer state-of-the-art care, screening and prevention services. With the renewed grant, the funding support is expanded to help encourage education and enrollment of Ben Taub Hospital patients in clinical trials and to recruit bilingual nurses and research coordinators.

“There is a great need for increased representation of minorities in clinical research,” said Rimawi.

In addition to providing care to breast cancer patients at the Baylor Clinic, physicians in the Smith Breast Center, including Rimawi and Drs. Kent Osborne, Julie Nangia and Sao Jiralerspong at BCM, provide care to more than 2,800 patients every year at Ben Taub Hospital’s breast center.

Other funding support of the Ben Taub Hospital breast clinic includes the Smith Foundation, Avon Foundation and Pink Ribbons Project.

Komen Houston will also recognize 21 other local organizations who have received 2011 grants at the Impact Awards luncheon to be held Tuesday, June 7, at 11:30 a.m. at the InterContinental Houston.

For more information on sponsorship or to buy tickets for the luncheon, visit the Komen web site. More information on Komen Houston and the grant process may also be found on www.komen-houston.org.

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On the Net:

• BCM

New cell therapy to prevent organ rejection could remove the need for life-long medication and boost the longevity of a transplant for patients

Researchers at King’s College London have used cells found naturally in the body, to re-educate the immune system to prevent rejection of an organ transplant while remaining capable of fighting infections and cancer.

Currently, patients must take immunosuppressant drugs to prevent a new organ from being rejected after transplantation. However, these drugs suppress the entire immune system, leaving the patient susceptible to infections and tumours.

Scientists say this new approach using immune cells, called regulatory T cells (Tregs), from the body could eliminate the need for immunosuppression, as the Tregs used will only suppress the activity of those cells which will attack the new organ, rather than suppress the whole immune system. The team says these results are encouraging. Ultimately this approach could extend the life of a transplanted organ and in turn, could alleviate the organ shortage problem.

The study, to be published in Science Translational Medicine, was carried out at King’s by scientists in its Medical Research Council Centre for Transplantation. King’s College London is part of King’s Health Partners Academic Health Sciences Centre, a pioneering collaboration with NHS Trusts which aims to ensure that the latest research in health is used to improve patient care at the earliest opportunity.

The study was part-funded by the British Heart Foundation and the Wellcome Trust.

Tregs are known to control the activity of many different immune cells, including T effector cells, which are responsible for mounting immune responses against foreign organisms, such as bacteria during an infection, and an organ following transplantation. The team have developed a method to select Tregs that can regulate only the activity of effector cells that would target a transplanted organ (“specific” Tregs), leaving the remaining effector cells to function normally.

Using a humanised mouse, where a mouse lacking its own immune system was given human effector cells and Tregs, the team were able to test the ability of these “specific” Tregs to prevent rejection of human skin grafted onto the mouse. The team found that the “specific” Tregs were significantly more potent than non-specific Tregs (those able to inhibit all effector cells) in protecting skin grafts from immune damage.

Professor Robert Lechler, Vice-Principal for Health at King’s and Executive Director of King’s Health Partners, said: ‘This study is a promising step forward that could lead to dramatic advances in preventing organ rejection and improving the quality of life of transplant patients.

‘Researchers at King’s are in a unique position. On average it takes 17 years for research discoveries and medical breakthroughs to become routine clinical practice. But being an Academic Health Sciences Centre means that researchers work directly alongside clinicians at leading NHS Foundation Trusts to speed up the time it takes for research to get from bench to bedside. Because of this, we hope to begin first-in-man trials within five years and could see patients being given this novel cellular therapy in around ten years time.’

If this approach were to be adopted to treat patients, blood would be sampled from a patient who will be receiving a transplant and their Tregs extracted from it. These Tregs would then be mixed with cells from the selected organ donor and the “specific” Tregs isolated using the new method developed by the team. The specific Tregs would then be expanded in numbers in a specialised sterile laboratory and be reintroduced into the patient after the transplant. Scientists believe this therapeutic approach will be applicable to the majority of solid organ transplants such as the kidney, heart and liver.

The King’s study is one of three papers in Science Translational Medicine reporting progress towards immune cell therapies to prevent transplant rejection. Together, they make it possible to see how such therapies might work, if successfully developed.

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On the Net:

• King’s College London

Researchers at the University of Granada have found that goat milk has nutritional characteristics beneficial to health. They have determined that goat milk has many nutrients that make it similar to human milk

The research group AGR 206 at the University of Granada Department of Physiology and Institute of Nutrition and Food Technology “Jose Matáix”, coordinated by professor Margarita Sánchez Campos, have proven that goat milk has nutritional characteristics beneficial to health.

The regular consumption of goat milk by individuals with iron deficiency anemia improves their recovery, since it enhances the nutritional use of iron and enhances the regeneration of hemoglobin; this means that this type of milk minimizes calcium and iron interactions. Conversely, this type of milk protects DNA stability, even in cases of iron overload caused by prolonged treatments with this mineral to treat anemia.

University of Granada researchers have found that goat milk has many nutrients ““as casein”“ that make it similar to human milk. Goat milk contains less casein alpha 1 ““as human milk”“, which is responsible for most allergies to cow milk. Therefore, goat milk is hypoallergenic. “For this reason, in some countries it is used as the basis for the development of infant formula in place of cow milk”, University of Granada researchers point out.

Additionally, another beneficial aspect of goat milk is that it contains a significant amount of oligosaccharides. Goat milk has more oligosaccharides with a composition similar to that of human milk. These compounds reach the large intestine undigested and act as prebiotics, i.e they help develop probiotic flora that competes with pathogenic bacterial flora, making it disappear.

Less lactose

Similarly, goat milk contains a lower proportion of lactose than cow milk ““about 1% less”“ and, as it is easier to digest, individuals with intolerance to this milk sugar can tolerate goat milk”.

The essential difference between the composition of cow and goat milk stems from the nature of their fat content: it is not only the small size of goat milk’s blood cells, but rather the profile of its fatty acids. Goat milk contains more essential fatty acids (linoleic and arachidonic) than cow milk. Both belong to omega-6 series. Similarly, goat milk has 30-35% medium-chain fatty acids (C6-C14) MCT, while cow milk has only 15-20%. These fatty acids are a quick source of energy and are not stored as body fat. In addition, goat milk’s fat reduces total cholesterol levels and maintains adequate levels of triglycerides and transaminases (GOT and GPT). This makes it a food of choice for the prevention of heart diseases.

As regards their mineral composition, University of Granada researchers point out that goat milk is rich in calcium and phosphorus “it is highly bioavailable and favors their deposition in the organic matrix of bone, leading to an improvement in bone formation parameters”. It also has more zinc and selenium, which are essential micronutrients contributing to the antioxidant defense and for the prevention of neurodegenerative diseases.

For all these reasons, researchers consider that “goat milk can be considered natural functional food, and its regular consumption should be promoted among the population in general, specially among those with allergy or intolerance to cow milk, malabsorption, high cholesterol levels, anemia, osteoporosis or prolonged treatments with iron supplements”.

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On the Net:

• UGR

Researchers studying the life threatening infectious disease sepsis have discovered how the infection can lead to a fatal inflammatory response through blood vessel cells. The research, which is published in EMBO Molecular Medicine, focuses on blocking crucial Matrix Metalloprotease enzymes (MMP) which activate the response.

Sepsis, and the associated systemic inflammatory response syndrome (SIRS), is a deadly condition caused by an infection of the blood which leads to whole-body inflammation. The condition is a major cause of death in intensive care wards worldwide and is most common in elderly and critically ill patients, as well as patients who are immunocompromised.

“Sepsis is a deadly disease, yet the underlying mechanisms which allow it to change body functions remains poorly understood and this has blocked the advancement of potential treatments,” said lead author Athan Kuliopulos, from Tufts Medical Center and Tufts University School of Medicine, Boston. “One such mechanism is the inability of the body to regulate the inflammatory-coagulation response to the infection, which can seriously damage the patient.”

The team focused their research on Matrix Metalloprotease-1 (MMP-1) which plays a key role in the immune systems response to invading pathogens and infectious diseases, but can cause uncontrolled tissue damage, which threatens the life of patients.

The study revealed how human sepsis patients have been found to have elevated levels of proMMP-1 and active MMP-1 in blood plasma which predicted both early and late death at 7 and 28 days after diagnosis.

By studying infected mice the team examined how MMP-1 was released from endothelial cells, the thin layer of cells which cover the interior surface of blood vessels. The team found that the blocking of MMP-1 activity suppressed endothelial barrier disruption, helped prevent lung failure, and improved survival in mice.

“We made the discovery that MMP-1, and its mouse equivalent MMP-1a, activates protease-activated receptors which contribute to the pro-inflammatory response of the body to sepsis through endothelial cells,” said Kuliopulos. “By blocking the mouse MMP-1 we significantly improved the survival of the mice thus demonstrating a dependence on MMP-1.”

The findings reveal MMP-1 to be an important early activator and suggest that therapeutics which target MMPs may prove beneficial in the treatment of sepsis.

“Sepsis remains a common, difficult to manage and stubbornly persistent syndrome when caring for critically ill patients,” said Kuliopulos. “This discovery that MMP-1 acts as an activator provides us with a blueprint to investigate entirely new types of treatment for sepsis patients.”

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On the Net:

• Wiley-Blackwell
• EMBO Molecular Medicine

A new study has found that there is no physical explanation for delusional infestations, and those patients who complained of being infected with bugs or eggs generally had a clean report on medical exams.

According to the Centers for Disease Control and Prevention, people who suffer from delusional infestation have also reported fatigue, joint pain, and short term memory loss.

In cases of delusional infestation, “patients often complain that the physician isn’t examining their skin closely enough to see the infesting organisms,” Dr. Mark Davis of the Mayo Clinic in Rochester, Minnesota, told Reuters Health.

“This study indicates that even when skin biopsies are obtained, and specimens of the organisms brought by the patients are carefully examined, there is no objective evidence of skin infestation,” added Davis, who worked on the new study.

The researchers reviewed the cases of 108 patients who were diagnosed with delusional infestation at the Mayo Clinic between the years 2001 and 2007.

According to a report published in Archives of Dermatology, all of those patients believed they were infested with bugs, worms, or inanimate objects, and complained of different skin irritations.

Doctors did a biopsy on 80 of those patients to look more closely at the skin.

“This study is important for patients,” the authors wrote in a statement. “Patients frequently believe that physicians are dismissive of their concerns and are not examining their skin closely enough, and therefore patients request that more testing be performed. This showed that biopsy results do not change a physician’s clinical diagnosis of delusional infestation.”

Over half of the biopsies did show dermatitis, a skin condition marked by inflammation and red and itchy skin.  However, the researchers said they were unsure if that could be leading to patients’ symptoms and beliefs that they were infested, or if their skin was inflamed due to them scratching.

A patient’s symptoms in one case were partially explained by an underlying medical condition.  The patient had rectal itching and tingling that turned into a crawling sensation.  She was eventually diagnosed with the virus that causes herpes.

Davis said reports show that some patients with a delusional infestation may have other medical or psychiatric conditions.

The CDC has been researching how common delusional infestation is, as well as what type of people tend to report symptoms.

“It is an unexplained and debilitating illness of unknown cause,” a CDC spokesperson told Reuters Health. “We recognize that…healthcare providers are perplexed and frustrated” and patients and their families are suffering, the spokesperson added.

Davis said it is important for doctors to take a patient’s history and do a physical exam if they suspect delusional infestation but are not positive.

“If there is any possibility that the patient’s complaints/concerns could be explained by anything other than delusional infestation, then all relevant tests should be done,” he said in a statement.

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On the Net:

• CDC
• Mayo Clinic
• Archives of Dermatology

Infections lead to higher bills, extended hospital stays, risk of readmission

Obese patients undergoing colon surgery are 60 percent more likely to develop dangerous and costly surgical-site infections than their normal-weight counterparts, new Johns Hopkins research suggests.

These infections, according to findings published in the journal Archives of Surgery, cost an average of $17,000 more per patient, extend hospital stays and leave patients at a three-times greater risk of hospital readmission.

“Obesity is a leading risk factor for surgical-site infections, and those infections truly tax the health care system,” says Elizabeth C. Wick, M.D., an assistant professor of surgery at the Johns Hopkins University School of Medicine and the lead author of the study. “The burdens of caring for obese patients need to be better recognized.”

To conduct the study, the Johns Hopkins team analyzed claims data from eight different Blue Cross and Blue Shield insurance plans for partial or total colon removal surgeries performed on adults ages 18 to 64 between 2002 and 2008. They identified 7,020 patients, 1,243 of whom were obese. The researchers looked at 30-day infection rates and calculated total costs from all health care claims for 90 days following surgery.

Colon surgery “” performed to treat colon cancer, diverticulitis and inflammatory bowel disease “” costs roughly $300 more per obese patient, whether an infection occurred or not. Obese patients also had slightly longer hospital stays, regardless of infection.

The average cost of caring for a patient with a surgical-site infection was $32,182 compared to $15,131 for each patient who didn’t get infected. Those with infections stayed in the hospital for an average of 9.5 days compared to 8.1 days for those who did not contract one. The probability of hospital readmission in infected patients was 27.8 percent versus 6.8 percent in non-infected patients. When they had to be readmitted, those who had surgical-site infections stayed an average of two days longer than those without.

Not only are these findings relevant to physicians who need to pay special heed to infections in heavier patients but, the authors argue, to policymakers who plan to mandate public reporting of hospitals’ surgical-site infection rates. Some insurers, meanwhile, have begun to withhold payment from hospitals when patients develop these complications and other insurers have discussed similar penalties. None of these plans take into account the higher infection rates found in obese surgical patients, Wick says.

Wick and her colleagues worry that punishing hospitals for surgical-site infections in obese patients could lead to discrimination, with surgeons shying away from operating on the heaviest patients for fear of financial loss and public shaming. Hospitals in 2012 will be required to publicly release surgical-site infection rates. If a hospital treated fewer obese patients, she notes, it would likely have fewer reportable infections.

“Pay-for-performance policies in surgery should account for the increased risk of infection and the cost of caring for this population,” she says. “Failure to consider these differences can lead to perverse incentives that may penalize surgeons who care for obese patients and may even affect obese patients’ access to surgery.”

Thirty-four percent of adults in the United States are now estimated to be obese (those with a body mass index above 30), up from just 15 percent a decade ago.

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On the Net:

• Johns Hopkins Medical Institutions
• Archives of Surgery

Patients who undergo a procedure to unblock a coronary artery are more likely to survive longer if they participate in structured follow-up care, according to research in Circulation: Journal of the American Heart Association.

In their 14-year analysis, researchers discovered a 46 percent relative reduction in death from all causes in patients who participated in cardiac rehabilitation following angioplasty.

The study focused on patients treated with percutaneous coronary interventions (PCI), commonly known as angioplasty. Using data from a Mayo Clinic registry of PCI patients, along with telephone follow-up, the researchers examined outcomes for almost 2,400 patients who underwent a first PCI in the Rochester, Minn., area from 1994 to 2008, and survived their hospital stay.

In PCI, a physician inflates a balloon on a catheter tip to flatten plaque in the artery against the vessel wall. In many cases, they also insert a stent (metal-mesh tube) to prop the vessel open.

Forty-percent of the patients had participated in at least one session of a cardiac rehabilitation program, and participants attended an average of 13.5 sessions. Such programs can boost survival rates after heart attacks and systematically provide lifestyle interventions and treatments to improve recovery and long-term health of heart patients.

“Our findings show that patients who participate in cardiac rehabilitation following PCI have better long-term survival “” about 50 percent better “” than those who don’t participate in cardiac rehabilitation,” said Randal Thomas, M.D., M.S., lead author of the study and director of the Mayo Clinic’s Cardiovascular Health Clinic in Rochester, Minn.

The results accounted for smoking status, obesity, high cholesterol, family history, and certain medical conditions that might affect life expectancy, such as heart failure, kidney disease, or diabetes. The researchers noted a difference in death rates starting at one year of follow-up. Improved outcomes were among men and women, older and younger patients, and in patients who had undergone elective or non-elective PCI.

Almost 400 patients had subsequent heart attacks and 755 had additional procedures to open blocked vessels. In all, 503 patients died during follow-up; 199 of the deaths were validated as being cardiac-related.

Physicians and patients should understand that PCI is an important treatment, but not a cure for heart disease, and that ongoing interventions after PCI can help patients live longer, healthier lives, Thomas said. Cardiac rehabilitation programs include patient education, monitored and personalized exercise training, nutrition counseling, smoking cessation support, weight control therapy, and medical evaluations to track patient progress, symptoms, medication side effects and medication adherence.

“Cardiac rehabilitation programs are effective at improving recovery, quality of life and long-term survival because they help deliver the lifestyle and medication therapies that have been shown to slow or even reverse the process of heart disease,” Thomas said.

Because the study was observational rather than randomized, researchers used three statistical techniques to account for factors that might bias their results. For example, younger, healthier, more motivated patients who were already more likely to live longer were also more likely to participate in cardiac rehabilitation.

Although the study population was predominantly white, the results are consistent with other studies of cardiac rehabilitation in other patient subgroups with cardiovascular disease that have included larger groups of non-white patients, Thomas said. He said the study results should be further validated in other patient populations.

More than 600,000 PCI procedures are performed in the United States annually, according to the American Heart Association.

Cardiac rehabilitation is recommended in the 2005 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions Guideline Update for PCI. But only about one-quarter of eligible U.S. patients participate, the researchers said. Gains in long-term survival would be substantial if all eligible PCI patients received cardiac rehabilitation, Thomas said.

Even in the unlikely event that the study results overestimate the true impact of cardiac rehabilitation and such services reduced deaths within five years by only 20 percent to 30 percent (instead of 46 percent, as found in the study), its impact on survival would still be substantial for patients after PCI, he said.

Most insurance companies cover up to 36 sessions of cardiac rehabilitation following PCI, heart attack and some other heart conditions. Medicare, which approved coverage of the programs for PCI patients beginning in 2006, typically covers 80 percent of the costs.

Participation by patients following PCI appears to have increased since the Medicare change in 2006, although Thomas said many doctors and patients still remain unaware that coverage for cardiac rehabilitation is available following PCI.

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On the Net:

• American Heart Association
• Circulation

Concern over vaccine safety is one of the primary factors preventing parents from having their asthmatic children vaccinated for influenza, or flu, according to Michigan researchers. Parents who do not vaccinate their children are also less likely to view flu as a”trigger” for their child’s asthma, the researchers noted.

The study will be presented at the ATS 2011 International Conference in Denver.

“When school starts in the fall, and during the winter season, many parents start dreading the cold and flu season,” said lead author Toby Lewis, MD, MPH, assistant professor of pediatric pulmonology at C.S. Mott Children’s Hospital in Ann Arbor, Mich. “This is particularly true for parents of children with asthma, who recognize that ‘a little cold’ can quickly trigger an asthma attack. Fortunately, there is something that can be done to reduce the chances of getting sick from influenza, one of the common winter viruses, and that is getting a vaccination to help prevent this infection. “

Influenza vaccination is recommended for all children, but especially for children with asthma to help prevent asthma exacerbations or ‘flares,'” Dr. Lewis added.”Despite this recommendation, vaccination rates remain low. The reasons for under-immunization are poorly understood.”

To determine parental attitudes toward the flu vaccine, and learn the reasons why some parents do not have their asthmatic children vaccinated, the researchers conducted a national survey from August 13 ““ Sept 7, 2010 of 1,621 parents; 237 parents indicated at least one child had asthma and were included in the final compilation of data.

“The parents included in the study were ethnically diverse and were from a broad spectrum of economic backgrounds,” Dr. Lewis noted.

Of those surveyed, 70 percent reported that they vaccinated their child against seasonal or H1N1 influenza during the prior winter season (2009-2010), and 65 percentstated that they planned to have their child vaccinated against influenza in the upcoming season (2010-2011), indicating consistency in vaccination behavior. The study also found that parents who did not vaccinate their asthmatic children against influenza were less likely than those that did vaccinate indicate that getting a viral infection was a “very important” trigger of their child’s asthma (53 percent vs. 72 percent), and were more likely to be concerned about vaccine side effects (60 percent vs. 26 percent) and getting sick from the vaccine itself (41 percent vs. 13 percent).

“Not surprisingly, parents who felt that their children were likely to experience an asthma attack when they got a respiratory infection were more likely to get their child vaccinated,” Dr. Lewis said. “Worries about potential side effects of the vaccine emerged as an important factor for families who did not have their child vaccinated. The group as a whole indicated that their physician was an important source of health information for their family ““ suggesting that physicians may have an opportunity to advise families about this important preventative measure.”

The survey also identified exposures in addition to colds and flu that parents believe are most likely to trigger asthma attacks, including:

    * exposure to smokers (73 percent);
    * exposure to outdoor allergens such as pollen and weeds (81 percent);
    * outdoor air quality/pollution levels (77 percent);
    * exposure to indoor allergens such as dust mites and cockroaches (71 percent)
    * contact with furry or hairy animals (48 percent); and,
    * food(30 percent).

Dr. Lewis noted that the study provides helpful insight into the way families of children with asthma view influenza infection and the influenza vaccine.

“The results will help physicians, public health professionals and health educators tailor messages most effectively to this group of families,” she said.”We will continue to analyze our current survey results to better understand parent attitudes, and hope to work with colleagues to develop educational messages specifically designed for parents who have previously opted out of vaccinating their children against influenza ““ for instance, highlighting stories from parents of children with asthma who did get their child vaccinated to help show a positive experience with influenza vaccination.”

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On the Net:

• American Thoracic Society

Scientists from Schepens Eye Research Institute are the first to regenerate large areas of damaged retinas and improve visual function using IPS cells (induced pluripotent stem cells) derived from skin. The results of their study, which is published in PLoS ONE this month, hold great promise for future treatments and cures for diseases such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and other retinal diseases that affect millions worldwide.

“We are very excited about these results,” says Dr. Budd A. Tucker, the study’s first author. “While other researchers have been successful in converting skin cells into induced pluripotent stem cells (iPSCs) and subsequently into retinal neurons, we believe that this is the first time that this degree of retinal reconstruction and restoration of visual function has been detected,” he adds. Tucker, who is currently an Assistant Professor of Ophthalmology at the University of Iowa, Carver College of Medicine, completed the study at Schepens Eye Research Institute in collaboration with Dr. Michael J. Young, the principle investigator of the study, who heads the Institute’s regenerative medicine center.

Today, diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are the leading causes of incurable blindness in the western world. In these diseases, retinal cells, also known as photoreceptors, begin to die and with them the eye’s ability to capture light and transmit this information to the brain. Once destroyed, retinal cells, like other cells of the central nervous system have limited capacity for endogenous regeneration.

“Stem cell regeneration of this precious tissue is our best hope for treating and someday curing these disorders,” says Young, who has been at the forefront of vision stem cell research for more than a decade.

While Tucker, Young and other scientists were beginning to tap the potential of embryonic and adult stem cells early in the decade, the discovery that skin cells could be transformed into “pluripotent” cells, nearly identical to embryonic cells, stirred excitement in the vision research community. Since 2006 when researchers in Japan first used a set of four “transcription factors” to signal skin cells to become iPSCs, vision scientists have been exploring ways to use this new technology. Like embryonic stem cells, iPSCs have Âthe ability to become any other cell in the body, but are not fraught with the ethical, emotional and political issues associated with the use of tissue from human embryos.

Tucker and Young harvested skin cells from the tails of red fluorescent mice. They used red mice, because the red tissue would be easy to track when transplanted in the eyes of non-fluorescent diseased mice.

By forcing these cells to express the four Yamanaka transcription factors (named for their discoverer) the group generated red fluorescent IPSCs, and, with additional chemical coaxing, precursors of retinal cells. Precursor cells are immature photoreceptors that only mature in their natural habitat””the eye.

Within 33 days the cells were ready to be transplanted and were introduced into the eyes of a mouse model of retina degenerative disease. Due to a genetic mutation, the retinas of these recipient mice quickly degenerate, the photoreceptor cells die and at the time of transplant electrical activity, as detected by ERG (electroretinography), is absent.

Within four to six weeks, the researchers observed that the transplanted “red” cells had taken up residence in the appropriate retinal area (photoreceptor layer) of the eye and had begun to integrate and assemble into healthily looking retinal tissue.

The team then retested the mice with ERG and found a significant increase in electrical activity in the newly reconstructed retinal tissue. In fact, the amount of electrical activity was approximately half of what would be expected in a normal retina. They also conducted a dark adaption test to see if connections were being made between the new photoreceptor cells and the rest of the retina. In brief, the group found that by stimulating the newly integrated photoreceptor cells with light they could detect a signal in the downstream neurons, which was absent in the other untreated eye.

Based on the results of their study, Tucker and Young believe that harvesting skin cells for use in retinal regeneration is and will continue to be a promising resource for the future.

The two scientists say their next step will be to take this technology into large animal models of retinal degenerative disease and eventually toward human clinical trials.

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On the Net:

• Schepens Eye Research Institute

What if you were told you carried a gene that increases your risk for Alzheimer’s disease? And what if you were told this gene starts to do its damage not when you’re old but when you’re young?

Brace yourself.

Scientists know there is a strong genetic component to the development of late-onset Alzheimer’s. In 1993, researchers discovered a gene known as ApoE4 “” carried by about a quarter of us “” that triples the risk for getting Alzheimer’s. In 2009, three more risky genes were discovered, and one of them, called clusterin, or CLU, was found to up the risk of getting Alzheimer’s by another 16 percent.

But nobody could explain what the CLU gene actually did. Now, UCLA researchers know, and the explanation is a doozy: This risk gene begins to damage your brain a full 50 years before people normally get Alzheimer’s.

In the current online edition of the Journal of Neuroscience, Paul Thompson, a UCLA professor of neurology, and his colleagues report that the C-allele of the CLU gene (an allele is one of two or more forms of a gene), which is possessed by 88 percent of Caucasians, impairs the development of myelin, the protective covering around the neuron’s axons in the brain, making it weaker and more vulnerable to the onset of Alzheimer’s much later in life.

The researchers scanned the brains of 398 healthy adults ranging in age from 20 to 30 using a high-magnetic-field diffusion scan (called a 4-Tesla DTI), a newer type of MRI that maps the brain’s connections. They compared those carrying a C-allele variant of the CLU gene with those who had a different variant, the CLU T-allele.

They found that the CLU-C carriers had what brain-imaging researchers call lower “fractional anisotropy” “” a widely accepted measure of white-matter integrity “” in multiple brain regions, including several known to degenerate in Alzheimer’s. In other words, young, healthy carriers of the CLU-C gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing the disease later in life.

The discovery of what this gene does is interesting on several levels, said Thompson, the senior author of the study.

“For example, Alzheimer’s has traditionally been considered a disease marked by neuronal cell loss and widespread gray-matter atrophy,” he said. “But degeneration of myelin in white-matter fiber pathways is more and more being considered a key disease component and another possible pathway to the disease, and this discovery supports that.”

Thompson said four things are surprising with the discovery of this gene’s function:

   1. This risk gene damages your brain a full 50 years before people normally get Alzheimer’s. The damage can be seen on an MRI scan, but there are no symptoms yet.

   2. It’s now known what this mysterious gene does “” namely, make your brain wiring vulnerable to attack by impairing the wiring before any senile plaques or tangles develop.

   3. Rather than being a gene that few people have, a whopping 88 percent of Caucasians have it. “So I guess you could say the other 12 percent have an ‘Alzheimer’s resistance gene’ that protects their brain wiring,” said Thompson, who is also a member of UCLA’s Laboratory of Neuro Imaging and the UCLA Brain Research Institute.

   4. Finally, he said, knowing the role of this gene is useful in predicting a person’s risk of the disease and in seeing if you can step in and protect the brain in the 50-year time window you have before the disease begins to develop.

Of course, the obvious question is if most of us have this “bad” gene, why isn’t Alzheimer’s rampant in young people?

Less myelination in CLU-C carriers may not translate into poorer cognition in youth, said Thompson, because the brain can compensate. “The brain has a lot of built in redundancy “” miles and miles of brain connections,” he said. Still, he said, with the passage of time “” and when exacerbated by other factors, such as normal neuron death as we age and plaque and tangle development in the early stages of Alzheimer’s “” reduced myelin integrity could facilitate cognitive impairment.

“So it’s unlikely we are seeing the earliest possible signs of Alzheimer’s-associated brain changes in these young people,” Thompson said. “It’s more likely the reduced fiber integrity represents an early developmental vulnerability that may reduce brain resilience to later Alzheimer’s disease pathology. Inn other words, its mechanism of action may not be part of the classic Alzheimer’s pathways that lead to abnormal amyloid plaque and neurofibrillary tangle accumulation in the brain.”

The mapping of structural brain differences in those at genetic risk for Alzheimer’s disease is crucial for evaluating treatment and prevention strategies, Thompson said. Once identified, brain differences can be monitored to determine how lifestyle choices influence brain health and disease risk.

“We know that many lifestyle factors, such as regular exercise and a healthful diet, may reduce the risk of cognitive decline, particularly in those genetically at risk for Alzheimer’s, so this reminds us how important that is,” he said.

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On the Net:

• University of California – Los Angeles
• Journal of Neuroscience

Sugar has been found to be an effective and low-cost way to boost the effectiveness of antibiotics for chronic bacterial infections such as staph, strep, tuberculosis and urinary tract infections, researchers say.

James Collins, a professor of Biomedical Engineering at Boston University who is also a Howard Hughes Medical Institute investigator and a core faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, and his research team discovered that the simple compound sugar dramatically boosts the effectiveness of first-line antibiotics.

Chronic and recurring infections are often caused by bacterial “persisters” that manage to survive antibiotic treatment by shutting themselves down and metabolically going into hibernation.

Persister bacteria should not be confused with antibiotic-resistant bacteria, whose ability to withstand drug treatments is based on genetic mutations fostered by drug treatment.

Although persisters are genetically identical to other members of the bacterial community, they separate themselves by their ability to switch into a power-saving mode.

Initially, the patient seems to be fully recovered, only to have the bacteria return after several weeks or months, but this time possibly more aggressive than ever and the patient goes into a relapse.

Treatment of infectious diseases has been hindered by these persistent bacteria, allowing illnesses to stretch over several months, and can cause the infection to spread to other organs such as the kidneys, driving up medical costs.

Growing research in the area of bacterial persistence exists, yet no direct treatment for them has been discovered until Dr. Collins’ research team made their discovery.

Researchers tested Eschericia coli (E. coli) bacteria that causes common urinary tract infections and found that 99.9% of the persisters were eliminated within only two hours. The results were compared to no effect without sugar.

The researchers found that “a spoonful of sugar makes the medicine work.” Sugar is found to be an effective weapon to help stimulate the hibernating bacteria back into active status where they become vulnerable to the antibiotics.

The new approach adds sugar to the antibiotic, where the sugar acts as a stimulant to turn on the bacteria’s normal responses that can be killed by the antibiotic.

Professor Collins plans to further investigate the sugar additives effectiveness against tuberculosis, which kills about 4,700 people every day, according to the World Health Organization.

“Our goal was to improve the effectiveness of existing antibiotics, rather than invent new ones, which can be a long and costly process,” says first author on the study Kyle Allison of Boston University.

He adds that the findings have the potential to improve the lives of untold numbers of people who struggle with nagging infections, while also reducing healthcare costs substantially.

The findings can be found in the May 12 issue of Nature.

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On the Net:

• Boston University
• Nature