By Reed Miller

Medscape.com, January 5, 2010 (Amsterdam, Netherlands) – Results from the ongoing Amsterdam Resuscitation Study (ARREST) showing a causal relationship between CPR chest compressions and ventricular fibrillation (VF) underscore the need for defibrillators that can accurately monitor the patients’ heart rhythm during chest compressions, according to researchers.

In their analysis published online December 30, 2009 in Circulation: Arrhythmia and Electrophysiology, in patients treated by first responders for out-of-hospital cardiac arrest, immediate resumption of chest compressions following defibrillation leads to earlier recurrence of ventricular fibrillation.

“Until this publication, the general idea was that chest compressions cannot cause refibrillation, and we have clearly shown beyond a doubt that it is not just coincidence but . . . a true relation between the moment we start chest compression and the fact that refibrillation occurs,” study coauthor Dr Rudolph Koster (University of Amsterdam, the Netherlands) told heartwire .

The study included patients treated by first responders with external defibrillators in North Holland presenting with VF as their initial rhythm. The responders tracked ECG and impedance signals. Only 136 out of the initial 361 patients considered for the study met the inclusion criteria. Patients were randomized to two different resuscitation techniques. For half of the patients, following a defibrillation shock, the responders performed postshock analysis and checked the patient’s pulse before resuming chest compressions, as suggested in the 2000 resuscitation guidelines. In the other half of the patients in the study, responders resumed chest compressions as soon as possible after defibrillation, as recommended in the 2005 guidelines.

In the group treated under the 2000 guidelines, rescuers resumed compressions an average of 30 seconds (range 21 to 39 seconds) after the first defibrillator shock that successfully terminated VF. In the group treated under 2005 guidelines, compressions were resumed an average of eight seconds (range seven to nine seconds) after the shock (p<0.001).

VF recurred, on average, after 40 seconds (range 21 to 76 seconds ) in the delayed-compressions group vs 21 seconds (range 10 to 80 seconds) in the immediate-compressions group (p=0.001). The time interval between start of the compressions and the recurrence of VF was six (range 0 to 67) and eight (range three to 61) seconds, respectively (p=0.88). The hazard ratio for VF recurrence during the first two seconds of CPR vs the hazard of VF in the period prior to resumption of compressions was 15.5, but after eight seconds of compressions, the hazard of VF recurrence was similar to the hazard of VF prior to resumption of compressions.

VF Recurrence Doesn’t Diminish Value of Compressions

The link between VF recurrence and chest compressions does not diminish their value, Koster emphasized. Previous research, reported by heartwire , shows that minimizing interruptions in compressions improves the patient’s chances of survival. “It was never our intention to suggest that we would not do chest compressions . . . because we are sure that chest compressions, even after defibrillation, are needed to get the patient back from cardiac arrest to a perfusing and pulsating rhythm,” Koster said. “What we identified was that these chest compressions have an adverse effect. . . . You may need more and more repeated defibrillations, because the recurrence of ventricular fibrillation does occur at a high rate.”

So the ideal solution, Koster explained, would be a defibrillator that can continue to accurately track a patient’s heart rhythm during chest compressions so that the responder knows when VF has recurred and can deliver another shock almost immediately. However, the compressions interfere with the device’s ability to monitor the heart rhythm and detect VF, so the responders have to halt compressions for about 30 seconds in order to get a “clean signal.”

“Many times paramedics believe they can look at the heart rhythm while chest compressions are going on, but we think that’s not true. You need an automated filtering technique to make a reliable judgment possible.”

Clinical Trials of Defibrillators With Signal Filters on the Horizon

Koster expects that very soon, several external defibrillator manufacturers will be introducing devices that are able to “filter” the distortion caused by compressions and provide a clean signal within a few seconds of a chest compression. With that device, the responders could charge the defibrillator while performing the chest compressions and then, if the patient goes into VF, take their hands off the chest for about two seconds and deliver a shock from the defibrillator before immediately resuming chest compressions again, Koster said. “Then the interruption [in compressions] is so minimal compared with what is happening now many times, where interruptions are up to 20 to 30 seconds, which is really not a good thing. But only two seconds of interruption may be a very good compromise” between immediately shocking the heart, which may retrigger VF, and a long interruption in chest compressions, which could reduce the patient’s chances of survival.

Koster said he knows of at least one company that may begin clinical trials of defibrillators with this type of signal filter within 2010. Unfortunately, the technology will probably not be sufficiently tested in time to be incorporated in the new resuscitation guidelines that are scheduled to be published in October 2010, according to Koster, who is one of the experts developing the new guidelines.

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References

  • 1. Berdowski J, Tijssen J, and Koster R. Chest compressions cause recurrence of ventricular fibrillation after the first successful conversion by defibrillation in out-of-hospital cardiac arrest. Circ Arrhythm Electrophysiol 2009; DOI:10.1161/CIRCEP.109.902114. Available at: http://circep.ahajournals.org. Abstract

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Authors and Disclosures

Journalist                                          

Reed Miller

Reed Miller joined theheart.org in 2009 after nearly a decade covering the medical technology industry, most recently as a senior editor for Elsevier’s The Gray Sheet. He has been to more FDA advisory panel meetings than he cares to count. At Elsevier, he has also contributed to In Vivoand The Pink Sheetand spent a year as a managing editor for HCPro in Marblehead, MA writing about drug and device industry regulation and compliance.

American Institute of Physics  –  Vascular surgeons can address peripheral artery disease by dissolving blood-blocking plaque concentrations with a vibrating catheter. Inserting the catheter into the blocked artery allows it to be maneuvered to the location of the clot, where it breaks down the plaque into small pieces that travel safely away, opening up passages large enough to allow blood to pass through freely, or to create space for a stent when required.

Millions of Americans may be at risk for heart attack or stroke and not even know it. A pain in your leg may be a sign of something much more serious — even fatal. Here is a new method to fight peripheral arterial disease (PAD).

Marjo Madden thought her age was catching up with her! “I couldn’t walk any more than 50 feet without sitting down,” Madden recalls.

But it wasn’t age. It was PAD that was slowing her down. “I had a very bad burning sensation in the calves of my legs,” Madden says.

Just as the blood flow in a heart attack patient is cut off by plaque, in PAD, blood flow throughout the body can be cut off. PAD is treated now with a balloon or stent, but for some patients the plaque is too hard, or there’s too much of it. Until now, these patients would face invasive surgery … or worse.

“They have to have something done,” Imran Mohiuddin, M.D., a vascular surgeon at Methodist DeBakey Heart Center in Houston,. “otherwise, they’re at risk of losing that limb. So this is sort of — we call it limb salvage.”

The FDA has approved a vibrating catheter that gives doctors another tool to help patients who are running out of options. “The catheter works like a miniature jack hammer inside the blood vessel, and it comes up against an inclusion and then it starts vibrating,” Dr. Mohiuddin explains. “Through its vibrations, it’s able to slowly burrow a hole.”

Sensors detect tissue, so even though the vibrating catheter is strong enough to break through plaster, it won’t go through tissue. “It breaks up the particles into very, very microscopic particles, as small as a red blood cell,” Dr. Mohiuddin explains.

Once the catheter is through, doctors will use angioplasty or a stent to keep the artery open. “Often times, we would have to just abandon that case and actually perform a bypass operation,” Dr. Mohiuddin says.

Recovery time is just a day and for patients like Madden, this could be one way to help stop the pain and get moving again!  I’m going to use it to the fullest,” Madden says.

The vibrating catheter was approved by the FDA for use in the legs. The next step is to get it approved for other arteries. Doctors in Europe are already using this procedure successfully in the heart.

ABOUT PAD: Peripheral artery disease is a condition that affects about 10 million people in the U.S. It often leads to severe blockage in the arteries, particularly in the lower leg. Such blockages reduce blood flow to the legs and feet, increasing the risk of infection, leg ulcers, gangrene and amputation. Those with PAD are also more at risk for other cardiovascular diseases, including heart attack and stroke.

ABOUT STROKES: The brain is made up of living cells that require a constant supply of nutrient- and oxygen-rich blood. Blockage or rupture of the blood vessels supply parts of the brain cause most strokes. A stroke occurs when brain tissue is deprived of blood and brain cells die from the lack of oxygen. Depending on which area of the brain is affected, a stroke can cause vision problems, speech problems, disability, even death.

Traditionally, treatment for stroke-causing diseases involves blood-thinning drugs to prevent clots, but for patients with severe blockage, this may not be sufficient. Some temporary blockages only last minutes or hours, leading to mini-strokes. Mini-strokes are a sign of a serious problem and can lead to a permanent stroke if left untreated.

WHAT CAUSES HEART ATTACKS? Heart attack is the leading cause of death in North and South America and in Europe. It is usually the result of prolonged hardening and narrowing of the arteries that direct blood into the heart. When blood vessels are healthy, oxygen-rich blood flows easily to all the muscles and organs of the body. But if they become clogged by the buildup of fatty deposits on vessel walls, blood can be cut off, killing heart muscle cells. This is called coronary heart disease, and it can lead to heart attacks or strokes.

Thomas Jefferson University  (Philadelphia)  –  Neurological surgeons at Jefferson Hospital for Neuroscience are among the first surgeons in the United States using an FDA-approved liquid system for treating wide-necked brain aneurysms, which could eventually replace current treatments.

Principal investigator Erol Veznedaroglu, M.D., associate professor of Neurological Surgery and director of the division of Neurovascular Surgery and Endovascular Neurosurgery, Thomas Jefferson University Hospital, is one of the few surgeons selected to explore the use of a liquid embolic (blocking) system to fill wide-neck brain aneurysms, which have a wide opening where the aneurysm arises from the artery or blood vessel. A brain aneurysm is a weakness in a major blood vessel that causes a portion of the vessel wall to balloon out. This abnormality puts an individual at risk should the aneurysm break open and bleed.

“A wide-neck brain aneurysm is relatively uncommon and occurs in about 25 percent of persons with brain aneurysms,” said Dr. Veznedaroglu. “Wide-neck aneurysms can be difficult to treat both surgically (brain surgery to clip off the aneurysm) and endovascularly (treatment done from within the blood vessel), which are methods used to treat other types of brain aneurysms.”

“The potential benefit of the liquid embolic system may be the complete or partial blockage of the blood supply to the aneurysm,” said Deborah L. August, M.D., MPH, director of Clinical Research in the department of Neurological Surgery, Jefferson. “It may also help to correct or lessen some symptoms.”

Current treatments for brain aneurysms include open brain surgery to clip the aneurysm and coil embolization or coiling, less–invasive surgical procedure. For coiling, a catheter is inserted into an artery in the groin, then advanced into the affected artery in the brain. X-rays are used to guide the catheter into the artery.

“Coils are the most commonly used embolization device but some wide-neck aneurysms have such a large opening that the coils may not stay inside the aneurysm sac,” said Dr. Veznedaroglu. “In this case, the coils can fall back into the blood vessel and block or partly block the blood flow.”

Researchers noted they are not recruiting patients, as this is not a clinical study.

Rather, this is a Humanitarian Use Device which is used to diagnose or treat a disease or condition that affects fewer than 4,000 individuals in the United States per year and for which no comparable device is available.

The Food and Drug Administration (FDA) allows physicians to use such a device under a Humanitarian Device Exemption, when a device maker chooses not to do formal research studies to test a product as it would be used to treat a smaller population of patients.

“Before the FDA gave the exemption, it looked at facts given by the maker of the device and decided that the likely risks of using the system are within reason, compared to the possible benefits of using this device and compared to other treatments for a wide neck aneurysm,” said Dr. August. “Research studies have not been done to show whether this system works for treating wide-neck aneurysms.”

By filling the aneurysm sac or pocket with the liquid, blood flow into the aneurysm is blocked, helping to prevent the aneurysm from rupturing or increasing in size.

This treatment is done endovascularly and essentially consists of inserting a catheter into the blood vessel to cut off the blood supply. The material is delivered by slow-controlled injection through a very micro-size catheter into the aneurysm under x-ray visualization. The catheter is initially inserted into a vessel in the groin area and threaded to the vessel where the aneurysm is located. The material enters the aneurysm as a liquid through the catheter and then begins to solidify from the outside to the inside with final solidification or embolization occurring within five minutes.

To be eligible for such a procedure, a patient must be 18 years or older, not have an intracranial stent and/or coils or severe liver or kidney disease. Women who are pregnant or nursing are also not eligible.

Neurologists Use GPS For The Brain As Guide In Surgery

American Institute of Physics  –  Neurosurgeons’ jobs are made easier by a 3-D CT scan produced by an advanced imaging system. It produces a computerized image of blood vessels and surrounding soft tissue, which can be rotated for viewing from any angle. Brain surgeries can be performed more smoothly because this real-time representation makes visualization of aneurysms and stents simpler.

Surgery is getting better and better and the tools used are getting smaller and smaller. What used to require large incisions and months of recovery is now done with tiny instruments. The latest 3-D technology makes brain surgery better and safer for patients suffering from a stroke or aneurysm.

“It’s a funny feeling to wake up, all of a sudden in a hospital, and you’ve got things stuck in you everywhere, and you’re thinking, ‘What the hell happened?!’ It’s like a horror movie,” Arlene Mikol said.

Mikol had a bleeding brain aneurysm — something people survive only half the time. She credits being alive to neurosurgons who used a new brain imaging technology. During surgery, doctors threaded tiny instruments through the leg artery up to brain vessels. The imaging system produces 3-D CT scan images in real time.

“Think about this; if you’re working on the roof of your house, without a flashlight, for example, how can you really repair something if you’re not seeing it very well?” asks Demetrius Lopes, a neurosurgeon from Rush University Medical Center.

With the standard angiogram, you need to take 50 different images. Now, the 3-D scan can be rotated to look from any angle and see 500 pictures from just one image. “That has an impact on how fast a procedure is and how safe that procedure is going to be done.”

Arlene knows how lucky she is and has a new perspective. She said she wants to live till 90 to see her grandchildren grow up.

“So I’m fighting it as long as I can. I’m going to fight it!” Mikol exclaims.

The system is also used for stroke patients. Other advantages to it: surgeons are able to see fine details like the shape of an aneurysm and the exact placement of a stent. Also, patients are exposed to less radiation and need less contrast dye, which can affect the kidneys.

BACKGROUND: For victims of stroke, every second counts. New technology at Rush University Medical Center (Chicago) helps surgeons treat the blood vessels in the brain faster and with less risk. The new neuroendovascular suite is equipped with the latest in advanced, 3D imaging and interoperative software, allowing surgeons to see the blood vessels and surrounding brain tissue in ways they could not before.

HOW IT WORKS: Neuroendovascular surgeons use a catheter and an image-guidance system to thread tiny instruments through the femoral artery in the leg up to the brain vessels. The new imaging system at Rush produces 3D CT scans rendered in real time. As the surgeon snakes the catheter through the twists and turns of the blood vessels, a computerized 3D image of the blood vessel and surrounding soft tissue can be rotated to view from any angle. The image is translucent allowing the surgeon to see exactly where the catheter is in the tiny blood vessels. It’s similar to having a GPS system guiding you to your destination, compared to trying to navigate by the stars.

BENEFITS: While the procedure is taking place, the surgeon can visualize fine details such as the shape of the aneurysm or the exact placement of a stent. With the ability to take CT images, the impact on other structures in the brain can be immediately detected and evaluated, such as complications like intracranial bleeding. In addition to visualizing the brain, it is crucial for surgeons to know how well the brain is functioning during the procedure. The new suite offers a unique neurophysiologic monitoring system. During surgery, the specialists can monitor the patient’s vision, sensation, and movement even while the patient is under general anesthesia.

ABOUT CAT SCANS: CAT (Computerized Axial Tomography) scans are similar to conventional X-ray imaging, but instead of imaging the outline of bones and organs, a CAT scan machine forms a full three-dimensional computer model of the inside of a patient’s body. Doctors can even examine the body one narrow slice at a time. The X-ray beam moves all around the patient, scanning from hundreds of different angles, and the computer takes all that information to compile a 3D image of the body.

By Nancy Fowler Larson

Medscape.com, January 7, 2010 – Most healthcare workers (HCWs) approve of mandatory influenza vaccines for hospital employees, and their numbers could be further boosted by giving opponents more information, according to a study released yesterday in the January 2010 issue of the Archives of Pediatrics & Adolescent Medicine.

“Influenza is responsible for an estimated 36,000 deaths and 226,000 hospitalizations every year in the United States,” write John D. Lantos, MD, from Children’s Mercy Bioethics Center, Children’s Mercy Hospital, Kansas City, Missouri, and colleagues. “The Centers for Disease Control and Prevention recommend that all [HCWs] receive an annual influenza immunization to protect themselves and their patients. Nevertheless, only 40% of HCWs in the United States get immunized every year.”

At greatest risk for influenza infection are children and the elderly. Although vaccination rates are greater at pediatric hospitals, some continue to have low rates even in high-risk units. With the eventual goal of protecting pediatric and other populations in hospital settings, the study sought to determine the level of support for mandated vaccinations among HCWs and to pinpoint differences in the beliefs and behavior of supporters vs opponents.

From April through mid-May 2009, 585 randomly selected physicians, nurses, and other hospital employees of Children’s Mercy Hospital completed a Web-based questionnaire regarding their immunization histories, knowledge of the vaccine, and attitudes toward compulsory vaccinations for HCWs.

70% Favor Mandatory Vaccination

The results showed that 70% of employees favored mandatory influenza vaccination for HCWs who had no medical contraindications. Of the 391 respondents in that category, 363 (94%) had been immunized and were also more likely to have had their own children vaccinated. Of the 81 participants who opposed a mandate (15%), 45 had been vaccinated (P < .001).

There was no significant difference between those for or against mandatory immunizations in the belief that influenza is a hazard for their pediatric patients (66.5% for and 62% against, respectively; P = .07). However, of those who disapproved of obligatory immunizations, 29% believed themselves to be at high risk of contracting influenza compared with 51% of those in favor of mandatory vaccination (P < .001).

According to the authors, HCWs should be immunized because:

  • They are at significant risk of contracting influenza, and thus at high risk of exposing patients to the disease.
  • They are role models whose behavior can influence patients and coworkers to get vaccinated.
  • Those who are not immunized and contract influenza miss work, which could decrease the level of patient care.

“For all of these reasons, one could see immunization as a duty of professionalism and, as the American Nursing Association suggests, ‘an ethical responsibility,’ even if it carries a small amount of risk,” the authors write.

The authors report several limitations to their study:

  • There is a possibility of greater participation by those who support a mandate.
  • Some questions regarding a mandate were theoretical and may not accurately predict behavior.
  • Responses regarding vaccinations of children were not validated.

Education May Reduce Number of Those Opposed

The researchers conclude that opponents of mandatory immunization fall into 2 categories: Those in one group fully comprehend the value and safety of widespread vaccinations but still favor individual choice, and those in the other segment have fears and misconceptions about the vaccine itself.

“Better education programs would reduce the size of this group,” the authors write.

Institutional mandates are ethically defensible for 3 reasons, according to the authors: the vaccine is effective, voluntary programs fall short, and compulsory immunization would likely improve patient safety. Furthermore, mandatory vaccination works, the authors stated. They cited a study published online in October 2009 by Infection Control and Hospital Epidemiology that found a 98% compliance rate in a multihospital healthcare system requiring influenza immunizations for HCWs.

The authors conclude that an important area of future study will be the effect of such mandates on hospital patients. “The next frontier will be demonstrating the success of the programs in terms of patient safety and quality of care,” the authors write.

The study was supported by Children’s Mercy Hospital. The study authors have disclosed no relevant financial relationships.

Source: Arch Pediatr Adolesc Med. 2010;164(1):33-37.

The Wall Street Journal, January 6, 2010, by Shirley S. Wang  —  Scientists looking for ways to repair damaged cartilage-a leading cause of osteoarthritis-are employing horses to test a new method of tissue regeneration that uses concentrated stem cells.

Constance Chu, an associate professor and director of the Cartilage Restoration Center at the University of Pittsburgh, and Lisa Fortier, an associate professor of large-animal surgery at Cornell University’s veterinary school, are testing the new procedure on former racehorses and rodeo horses to determine if it is more effective than a commonly used cartilage repair treatment in the U.S. called “microfracture.”

They are also looking for biological markers that could help doctors diagnose earlier patients with cartilage damage and indicate which ones may be most responsive to tissue regeneration.

Cartilage, the strong but flexible material that coats bones at the hip, knee and other joints, can be weakened with overuse and age, and can be permanently damaged when someone twists a knee on the soccer field or dislocates a shoulder. Cartilage that has been torn or injured doesn’t naturally grow back, and treatment options remain limited.

Over the long term, cartilage injury increases the risk of osteoarthritis, a painful chronic condition and the most common form of arthritis. It affects almost 27 million Americans, according to the Arthritis Foundation.

To decrease pain, improve functioning and slow the disease’s progression, osteoarthritis is usually treated through a combination of medication, physical therapy to strengthen muscles and improve flexibility, a weight-loss program, and splints and braces. In severe cases, patients may undergo arthroscopic surgery to repair cartilage tears and remove loose tissue, or joint-replacement surgery. Some alternatives to traditional therapy include the use of the supplement glucosamine, which research shows may promote cartilage repair and formation, and vitamins like C and E that may help slow cartilage erosion and reduce pain.

Yet there isn’t any good way of detecting cartilage breakdown until the cartilage is broken or lost or osteoarthritis develops. And though cartilage-repair surgery has improved over the years, the repaired scar tissue isn’t as strong as real cartilage and isn’t able to bear the same weight. Patients who get surgery at 20 years old-as athletes who get injured often have to do-may develop osteoarthritis in their 30s and 40s and need additional surgery.

For about two decades, Dr. Chu and other researchers in the field have been trying to improve treatment by regenerating cartilage tissue. While many scientists have been successful at creating new tissue in the lab, they haven’t been able to grow cartilage in humans. The main challenge is that the structure of cartilage, which is critical to its supporting weight, is hard to mimic, says Fei Wang, director of the Musculoskeletal Tissue Engineering and Regenerative Medicine Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., which funds many researchers working on cartilage regeneration.

“It’s easy to generate a piece of tissue, but it’s not so easy to generate a tissue that works,” says Dr. Wang.

Over the last 10 years, Dr. Chu has also been studying how to identify cartilage injury at a reversible stage-that is, before the surface breaks down-and how to treat damaged cartilage and osteoarthritis more effectively.

Consisting mostly of water, cartilage is made up of a tough scaffold structure that encloses the water, much like a water bed. If the structure of the cartilage is ruptured, its integrity is destroyed and the fluid escapes. Thus any regenerated tissue needs to include a structure capable of bearing weight.

Not only is cartilage repair difficult, but it is hard to diagnose as well. Patients don’t feel pain-cartilage doesn’t contain any nerve endings-and there aren’t good tools for detecting injury to it until it becomes permanently damaged. People often don’t know they have a problem until they develop a more-serious disease that causes pain after the cartilage has further eroded.

Yet damage is likely to occur immediately after injury. Last month, Dr. Chu published a study in the Journal of Sports Medicine showing that even when cartilage appears visually healthy after a trauma, many of the cells underneath the impact site quickly die. If there was a way of immediately detecting and treating the cartilage damage, these people could be spared years of arthritic pain and disability, she says.

Dr. Chu is studying new imaging techniques for early detection of cartilage damage. For example, optical coherence tomography, which provides a three-dimensional image by scattering light through tissue, potentially has the ability to give detailed images of cartilage but without damaging the tissue, says Dr. Chu. She published work on this imaging technique in the Journal of Orthopedic Research in October.

Dr. Chu is also researching better ways for surgeons to treat cartilage damage in humans. She and her collaborators at Cornell University, Colorado State University and University of California, San Diego, recently began a study-funded by $1.7 million federal grant-looking at a new way of promoting cartilage growth by studying horses.

With microfracture, which has been growing in popularity as a way to treat patients soon after acute injury, surgeons puncture tiny holes into the bone beneath the damaged cartilage, prompting blood and bone marrow to fill the holes. The theory is that some of the bone marrow contains stem cells-which are cells that can grow into different types of cells-and other growth-promoting cells in the blood, a process that generates cartilage-like scar tissue. But this tissue isn’t as strong and doesn’t work as well as real cartilage, and the long-term benefits of the surgery aren’t well researched, according to Ranjan Gupta, professor and chairman of orthopedic surgery at the University of California, Irvine.

Currently, “all of our best efforts create inferior tissue to what we are born with,” says Dr. Chu. Cartilage transplant appears to be effective in filling the damaged cartilage, but isn’t widely available because it is difficult to find healthy cartilage for use in the transplant. “Just because we can’t get [the tissue] perfect unless it’s through transplant doesn’t mean we shouldn’t keep trying to improve the repair,” says Dr. Chu.

In the current study, she and her colleagues hypothesize that the more stem cells that are used to repair cartilage at the site of the damage, the better the regeneration of the tissue should be. They first create a dime-sized cartilage injury in the horse’s stifle joints, which resemble the human knee, and then test two different ways of concentrating the stem cells after taking them from the horse’s own bone marrow to see if either is better than microfracture and how they compare with each other.

One experimental method involves taking bone marrow and immediately spinning the sample in a centrifuge to separate out the part where the stem cells are mostly likely to be, while removing as much of the extra fluid and materials found in bone marrow as possible. The benefit of this technique is that it can be done during the surgery and used in the treatment, says Dr. Chu. The second method entails taking the stem cells from the bone marrow and growing them in a laboratory, which should yield the best crop of stem cells but would take a lot longer and involve additional procedures, she says.

Each horse in the study will be examined at 10 days and three months post-surgery for signs of cartilage repair. So far, 11 out of a total 12 horses have had the surgery. By three months, the injury should be filled with new tissue, says Dr. Chu.

If the use of blood concentrate in the horses appears to repair cartilage better than microfracture, Dr. Chu plans to undertake a similar clinical study on humans, which she estimates would begin in about two years.

Johns Hopkins School of Medicine, January 6, 2010  –  Johns Hopkins University researchers have created biodegradable nanosized particles that can easily slip through the body’s sticky and viscous mucus secretions to deliver a sustained-release medication cargo.

The researchers say these nanoparticles, which degrade over time into harmless components, could one day carry life-saving drugs to patients suffering from dozens of health conditions, including diseases of the eye, lung, gut or female reproductive tract.

The mucus-penetrating biodegradable nanoparticles were developed by an interdisciplinary team led by Justin Hanes, a professor of chemical and biomolecular engineering in the Whiting School of Engineering at Johns Hopkins. The team’s work was reported recently in the Proceedings of the National Academy of Sciences. Hanes’ collaborators included cystic fibrosis expert Pamela Zeitlin, a professor of pediatrics at the Johns Hopkins School of Medicine and director of pediatric pulmonary medicine at the Johns Hopkins Children’s Center.

These nanoparticles, Zeitlin said, could be an ideal means of delivering drugs to people with cystic fibrosis, a disease that kills children and adults by altering the mucus barriers in the lung and gut.

“Cystic fibrosis mucus is notoriously thick and sticky and represents a huge barrier to aerosolized drug delivery,” she said. “In our study, the nanoparticles were engineered to travel through cystic fibrosis mucus at a much greater velocity than ever before, thereby improving drug delivery. This work is critically important to moving forward with the next generation of small molecule and gene-based therapies.”

Beyond their potential applications for cystic fibrosis patients, the nanoparticles also could be used to help treat disorders such as lung and cervical cancer, and inflammation of the sinuses, eyes, lungs and gastrointestinal tract, said Benjamin C. Tang, lead author of the recent journal article and a postdoctoral fellow in the Department of Chemical and Biomolecular Engineering.

“Chemotherapy is typically given to the whole body and has many undesired side effects,” he said. “If drugs are encapsulated in these nanoparticles and inhaled directly into the lungs of lung cancer patients, drugs may reach lung tumors more effectively, and improved outcomes may be achieved, especially for patients diagnosed with early stage non-small cell lung cancer.”

In the lungs, eyes, gastrointestinal tract and other areas, the human body produces layers of mucus to protect sensitive tissue. But an undesirable side effect is that these mucus barriers can also keep helpful medications away.

In proof-of-concept experiments, previous research teams led by Hanes earlier demonstrated that latex particles coated with polyethylene glycol could slip past mucus coatings. But latex particles are not a practical material for delivering medication to human patients because they are not broken down by the body. In the new study, the researchers described how they took an important step forward in making new particles that biodegrade into harmless components while delivering their drug payload over time.

“The major advance here is that we were able make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions, and that these particles can transport a wide range of therapeutic molecules, from small molecules such as chemotherapeutics and steroids to macromolecules such as proteins and nucleic acids,” Hanes said. “Previously, we could not get these kinds of sustained-release treatments through the body’s sticky mucus layers effectively.”

The new biodegradable particles comprise two parts made of molecules routinely used in existing medications. An inner core, composed largely of polysebacic acid (PSA), traps therapeutic agents inside. A particularly dense outer coating of polyethylene glycol (PEG) molecules, which are linked to PSA, allows a particle to move through mucus nearly as easily as if it were moving through water and also permits the drug to remain in contact with affected tissues for an extended period of time.

In Hanes’ previous studies with mucus-penetrating particles, latex particles could be effectively coated with PEG but could not release drugs or biodegrade. Unlike latex, however, PSA can degrade into naturally occurring molecules that are broken down and flushed away by the body through the kidney, for example. As the particles break down, the drugs loaded inside are released.

This property of PSA enables the sustained release of drugs, said Samuel Lai, assistant research professor in the Department of Chemical and Biomolecular Engineering, while designing them for mucus penetration allows them to more readily reach inaccessible tissues.

Jie Fu, an assistant research professor, also from the Department of Chemical and Biomolecular Engineering, said, “As it degrades, the PSA comes off along with the drug over a controlled amount of time that can reach days to weeks.”

Polyethylene glycol acts as a shield to protect the particles from interacting with proteins in mucus that would cause them to be cleared before releasing their contents. In a related research report, the group showed that the particles can efficiently encapsulate several chemotherapeutics, and that a single dose of drug-loaded particles was able to limit tumor growth in a mouse model of lung cancer for up to 20 days.

Hanes, Zeitlin, Lai and Fu are all affiliated with Johns Hopkins Institute for NanoBioTechnology. Other authors on the paper are Ying-Ying Wang, Jung Soo Suk, and Ming Yang, doctoral students in the Johns Hopkins Department of Biomedical Engineering; Michael P. Boyle, an associate professor in Pulmonary and Critical Care Medicine at the Johns Hopkins School of Medicine; and Michelle Dawson, an assistant professor at the Georgia Institute of Technology.

This work was supported in part by funding from the National Institutes of Health, a National Center for Research Resources Clinical and Translational Science Award, the Cystic Fibrosis Foundation, the National Science Foundation and a Croucher Foundation Fellowship.

The technology described in the journal article is protected by patents managed by the Johns Hopkins Technology Transfer office and is licensed exclusively by Kala Pharmaceuticals. Justin Hanes is a paid consultant to Kala Pharmaceuticals, a startup company in which he holds equity, and is currently a member of its board. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

BiologyNews.net, January 5, 2010  —  The early stages of Alzheimer’s disease are thought to occur at the synapse, since synapse loss is associated with memory dysfunction. Evidence suggests that amyloid beta (Aβ) plays an important role in early synaptic failure, but little has been understood about Aβ’s effect on the plasticity of dendritic spines.

These spines are short outgrowths of dendrites (extensions of neurons) that relay electrical impulses in the brain. A single neuron’s dendrite contains hundreds of thousands of spines, providing memory storage and transmission of signals across the synapse – the junction where such nerve impulses occur. Plasticity of these spines, or the ability to change and grow, is essential for the transmission of signaling in the brain.

Researchers led by Roberto Malinow, MD, PhD, professor of neurosciences and Shiley-Marcos Endowed Professor in Alzheimer’s Disease Research at the University of California, San Diego School of Medicine, have shed more light on how Aβ’s destructive effects on the brain are related to its impact on the plasticity of dentritic spines. Their study was published on December 27 in the journal Nature Neuroscience.

The researchers have shown that if Aβ is over-produced by either the pre-or post-synaptic side of the axon, it can cause destructive effects. Secondly, these effects are over a distances of about 10 microns of the neuron – affecting thousands and thousands of synapses.

“We found that amyloid beta affects structural and not just functional, plasticity,” said Malinow. “Normally, plasticity can be induced, which makes synapses stronger and bigger, but amyloid beta prevents this.”

According to Malinow, it also appears that continuous release of Aβ is required to prevent plasticity. “Even a short window of 30 to 60 minutes without Aβ secretion is enough to permit plasticity to occur,” he said. As Aβ’s effect on the dendritic spines – critical for memory – had been thought to be irreversible, this shows that there is a hope of change if scientists learn how to stop the secretion of Aβ at synaptic sites.”

“Our results show that the continuous production of Aβ at dendrites or axons acts locally to reduce the number and plasticity of synapses,” Malinow concluded.

Source : University of California – San Diego

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The Tasmanian Devil (Sarcophilus harrisii), also referred to simply as ‘the devil’, is a carnivorous marsupial now found in the wild only in the Australian island state of Tasmania. The Tasmanian Devil is the only extant member of the genus Sarcophilus. The size of a small dog, but stocky and muscular, the Tasmanian Devil is now the largest carnivorous marsupial in the world (after the recent extinction of the Thylacine in 1936). It is characterised by its black fur, offensive odour when stressed, extremely loud and disturbing screech, and viciousness when feeding. It is known to both hunt prey and scavenge carrion and although it is usually solitary, it sometimes eats with other devils.

 

 

BiologyNews.net, January 5, 2010  —  An international team of scientists led by a Cold Spring Harbor Laboratory (CSHL) investigator has discovered that the deadly facial tumors decimating Australia’s Tasmanian devil population probably originated in Schwann cells, a type of tissue that cushions and protects nerve fibers.

The discovery stems from the team’s effort to carry out a genetic analysis of tumor cells. Based on these data, the scientists have identified a genetic marker to accurately diagnose the facial cancers, called devil facial tumor disease (DFTD).

The findings, which open new avenues for research into treatments and vaccines, will appear in the journal Science on January 1. Elizabeth Murchison, Ph.D., of CSHL and the Australian National University, is lead author of the paper; the work was conducted with CSHL Professor and HHMI Investigator Greg Hannon, Ph.D., among others.

DFTD is a unique type of cancer that is transmitted from animal to animal via biting or other physical contact – one of only two cancers known to spread by this method, which transfers living cancer cells between individuals (the other cancer is found in dogs). The devils’ tumors are mostly found on the face and mouth, but often spread to internal organs. With no diagnostic tests, treatments or vaccines currently available, this aggressive disease could wipe out the Tasmanian devil species in 25 to 35 years.

“Our findings represent a big step forward in the race to save the devils from extinction,” says Murchison. The research has provided a method for scientists to distinguish between DFTD and other types of devil cancers. This could be critical in efforts to identify and isolate affected animals and contain the disease’s spread.

The team’s genetic analysis has confirmed that the tumors that spread from animal to animal are genetically identical – exact clonal copies, each having originated from a single line of cells. The team determined the identity of the originating cell by using advanced sequencing technology to uncover the tumors’ “transcriptome” – the complete set of genes that are turned on in tumor cells. Comparing this readout to that from other tissues, the team found that the tumors’ genetic signature best matched that of Schwann cells. How these nervous system cells spawned cancer is still a mystery.

“Now that we’ve taken a good look at the tumors’ genetic profile, we can start hunting for genes and pathways involved in tumor formation,” says Hannon. The team has also compiled a catalogue of devil genes that might influence the pathology and transmission of the tumor — information that will be very useful in designing vaccines and other therapeutic strategies.   Source : Cold Spring Harbor Laboratory

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Save the Tasmanian Devil

 

Tasmanian Devils, are dying from an infectious face cancer caused by industrial pollutants. The Tasmanian government needs money in order to save the species.