Gel Lets Doctors Fix Ruptured Blood Vessels without Sutures

Support structure: This latex tube has been treated with heated polaxamer to make it rigid. Doctors could use the gel during surgery to mend vessels with glue rather than sutures.
Credit: Nature

BIOMEDICINE

The new technique could make some delicate surgical procedures quicker and safer.

• BY ALLA KATSNELSON

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A synthetic, temperature-sensitive gel could help surgeons reconnect blood vessels more quickly, safely, and easily. The new gel, successfully tested in rats, could also enable more complex robotic surgery as well as minimally invasive surgery.  

There have been few advances in the art of reconnecting blood vessels since French surgeon Alexis Carrel received the Nobel Prize in 1912 for his method of sewing them together. About a decade ago, surgeon Geoffrey Gurtner found himself longing for a substance that could be poured into the tiny blood vessels he was struggling to reconnect in order to prop them open while he sewed them together. "A lot of surgeries require reconnecting vessels," he says. "For two-thirds of operations, this would be helpful."  

When Gurtner took a post at Stanford University, he partnered with a group of Stanford chemical engineers and biomaterials experts who adapted a substance called Poloxymer 407, which is already approved by the U.S. Food and Drug Administration for internal use, to do the job. 

The trick was to tweak the properties of the substance so that it changes from a liquid to a solid state a few degrees above body temperature. The group used a halogen lamp to heat up the area around a severed blood vessel in rats, added the poloxymer, and then sealed the two ends with surgical glue.

"The liquid turns into a solid, and then instead of a bunch of collapsible floppy pieces of linguini, you have something like pixie sticks," Gurtner says. After connecting them, "you're left with a scarless joint between the two blood vessels."

The group tested the technique in the aorta, as well as tiny, hard-to-reach, and oddly angled blood vessels, of rats. Not only was it five times faster than hand-sewing, the animals also had less scarring and inflammation up to two years later. The technique is described in a study published online in Nature Medicine.

Gurtner isn't the first to attempt such an approach. Roger Khouri, a plastic surgeon and microvascular surgeon based in Miami, patented a similar idea almost 20 years ago.

Khouri used a lipid-based substance that could be cooled to a solid state using cold water, and then dissolved at body temperature. But there were no glues available at the time that could be used in the body, so his team employed surgical staples. "I used the technique on patients, but it never really took off because those staples never held very well," he says.

Gurtner says he hopes to begin testing the technique in patients next year, but would like to improve the glue that his team used. "Having that glue be perfect is really going to make this a no-brainer for doctors," he says.   

But Bruce Klitzman, a biomedical engineer and microvascular physiologist at Duke University, cautions that even if it works as well in humans as the developers hope, it might not be fully embraced by vascular surgeons. "It may save them five or 10 minutes, and if so, they might do it, but then again, you may have flexibility with suture that you may not have with this approach," he says.

Time to reboot thinking on trans fats: Natural trans fats from dairy and beef are good

Not all trans fats are created equal and it’s time for a change in nutrition labels in North America to reflect this, particularly when it comes to dairy and beef products.

Posted by Biomechanism 

According to a scientific review published in the latest edition of Advances in Nutrition, natural trans fats produced by ruminant animals such as dairy and beef cattle are not detrimental to health and in fact show significant positive health effects. Some evidence even links these natural trans fats to reduced risk of cardiovascular disease and cancer.

“The body of evidence clearly points to a change needed in how nutrition labels are handled,” says Dr. Spencer Proctor, one of the review authors and Director of the Metabolic and Cardiovascular Diseases Laboratory at the University of Alberta in Canada. “Right now, in Canada and U.S. a substantial portion of natural trans fats content is included in the nutrition label trans fats calculation, which is misleading for the consumer. We need a reset in our approach to reflect what the new science is telling us.”

Consumers are bombarded on a regular basis about what they should and shouldn’t eat. Quite often fat is the primary target of what to avoid and trans fats in particular have a negative reputation. However, the scientific review in Advances in Nutrition reveals that consuming natural trans fats produced by ruminant animals has different health effects than consuming industrial trans fats, such as partially hydrogenated vegetable oils used in the preparation of some foods such as some baked goods.

As the scientific evidence mounts, there is slowly rising public awareness of this difference. A change in how trans fat information is presented on nutrition labels would be a huge step forward, says Proctor. In some European countries, for example, natural trans fat is not included in the nutrition label calculation. Another approach may be to have separate listings for industrial trans fats and natural trans fats.

By definition, ruminant trans fat is naturally-occurring, found in meat and dairy foods. Industrial produced trans fat is a component of partially hydrogenated vegetable oils, which have been highly associated with cholesterol and coronary heart disease.

According to the review, the naturally occurring trans fat has a different fatty acid profile than industrial trans fat, which contributes to its different physiological effects. Also, the amount of natural trans fat consumed has been relatively stable and much lower than the amounts consumed from partially hydrogenated oils that have been associated with adverse effects.

Researchers evaluated an evidence base from numerous epidemiological and clinical studies in the Advances in Nutrition review. Based on the promising findings to date, plans for new studies are gaining momentum to further investigate the health implications of natural ruminant-derived trans fats.

For example, one leading scientific program is headed by Proctor, who recently was approved for a $1 million research grant from the Alberta Livestock and Meat Agency (ALMA) to further this line of study over the next several years. This represents a continuation of strong support for research programs by the livestock industry in Alberta.

“With industry, science, regulators and other important groups in this area working together, we can continue to make strides to help the public better understand the health implications of natural ruminant trans fats,” says Proctor.

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The scientific review on natural trans fats in Advances in Nutrition is available at http://advances.nutrition.org/content/2/4/332.full.pdf+html .

Scientists create mammalian cells with single chromosome set

Researchers have created mammalian cells containing a single set of chromosomes for the first time in research funded by the Wellcome Trust and EMBO. The technique should allow scientists to better establish the relationships between genes and their function.

Posted by Biomechanism 

Caption: Scientists at the University of Cambridge bred mice with fluorescent green cells derived from haploid (single chromosome set) embryonic stem cells. Credit: Anton Wutz and Martin Leeb, University of Cambridge/Nature

Mammal cells usually contain two sets of chromosomes – one set inherited from the mother, one from the father. The genetic information contained in these chromosome sets helps determine how our bodies develop. Changes in this genetic code can lead to or increase the risk of developing disease.

To understand how our genes function, scientists manipulate the genes in animal models – such as the fruit fly, zebrafish and mice – and observe the effects of these changes. However, as each cell contains two copies of each chromosome, determining the link between a genetic change and its physical effect – or ‘phenotype’ – is immensely complex.

Now, in research published today in the journal Nature, Drs Anton Wutz and Martin Leeb from the Wellcome Trust Centre for Stem Cell Research at the University of Cambridge report a technique which enables them to create stem cells containing just a single set of chromosomes from an unfertilised mouse egg cell. The stem cells can be used to identify mutations in genes that affect the cells’ behaviour in culture. In an additional step, the cells can potentially be implanted into the mouse for studying the change in organs and tissues.

The technique has previously been used in zebrafish, but this is the first time it has been successfully used to generate such mammalian stem cells.

Dr Wutz, a Wellcome Trust Senior Research Fellowship, explains: “These embryonic stem cells are much simpler than normal embryonic mammalian stem cells. Any genetic change we introduce to the single set of chromosomes will have an easy-to-determine effect. This will be useful for exploring in a systematic way the signalling mechanisms within cell and how networks of genes regulate development.”

The researchers hope that this technique will help advance mammalian genetics and our understanding of the gene-function relationship in the same way that a similar technique has helped geneticists understand the simpler zebrafish animal model.

Understanding how our genetic make-up functions and how this knowledge can be applied to improve our health is one of the key strategic challenges set out by the Wellcome Trust. Commenting on this new study, Dr Michael Dunn, Head of Molecular and Physiological Sciences at the Wellcome Trust, says:

“This technique will help scientists overcome some of the significant barriers that have so far made studying the functions of genes so difficult. This is often the first step towards understanding why mutations lead to disease and, ultimately, to developing new drugs treatments.”

Aggressive medical therapy could help prevent stroke

To prevent a common type of stroke, intensive medical therapy could be better by itself than in combination with surgery that props open affected arteries. But it remains to be seen whether the apparent advantage will prove true over the long term.

Posted by Biomechanism 

A CT scan shows massive stroke. A stroke occurs when a blood clot either blocks an artery or a blood vessel, altering the flow of blood to the brain. As a result brain cells begin to die and brain damage proceeds. When the brain cells of a certain region die the abilities of that area are adversely affected and can even be lost. Implications of a stroke can include a loss of speech, movement, and memory.

The findings, from a national clinical trial conducted by University of Florida researchers and colleagues, will be published online in The New England Journal of Medicine online on Wednesday, Sept. 7.

Against expectations, the short-term risk of stroke and related death was twice as high in some cases for patients whose diseased arteries were widened via balloon angioplasty and stent insertion, compared with patients who received medical therapy alone. Although the 30-day risk of stroke for the stenting patients is concerning, long-term results could be more favorable, the researchers said.

“Five years from now, who will be doing better — the patients who are being medically managed, or those who received a stent?” said study co-author Michael F. Waters, M.D., Ph.D., director of the Shands at UF Stroke Program, who along with Brian L. Hoh, M.D., the William Merz associate professor of neurological surgery in the College of Medicine, led the UF portion of the trial.

The study will have a substantial impact on clinical practice and research, the researchers said, because it is the first randomized stroke trial to pit stenting against nonsurgical treatment for symptomatic intracranial atherosclerosis, a type of stroke caused by artery blockage in the brain. Early results clearly show that intensive medical management is key to improving health, the researchers said.

“This study provides an answer to a longstanding question by physicians — what to do to prevent a devastating second stroke in a high-risk population. Although technological advances have brought intracranial stenting into practice, we have now learned that when tested in a large group this particular device did not lead to a better health outcome,” said Walter Koroshetz, M.D., deputy director of the NIH National Institute of Neurological Disorders and Stroke, which funded the clinical trial.

Every 40 seconds, someone in the U.S. has a stroke. Stroke is the fourth leading cause of death and a leading cause of disability in the U.S. Almost 800,000 people a year have a new or recurring stroke, according to the American Heart Association. With higher than average rates of stroke and related deaths, parts of the southeastern U.S. are together termed the “Stroke Belt.”

Patients with the type of stroke known as symptomatic intracranial atherosclerosis do not respond well to existing treatments. One-quarter of those patients have another stroke within 12 months, and the risk of additional strokes continues in subsequent years. Doctors are unsure what the best course of treatment is.

To find out, the UF researchers and colleagues launched a clinical trial, nicknamed SAMMPRIS, at 50 sites around the country, including at the Medical University of South Carolina, the lead site. The study recruited 451 participants age 30 to 80 who had at least 70 percent narrowing in the arteries in the brain, and had experienced symptoms within the previous 30 days. UF recruited the second-highest number of patients among all sites, through its stroke program, which has been designated a Comprehensive Stroke Center by the Agency for Health Care Administration.

Patients in one group were randomly assigned to receive intensive management involving smoking cessation and medications for blood pressure, cholesterol, diabetes and blood-clot prevention. A second group of patients had that same medical treatment but also had balloon angioplasty and stent implantation into the affected brain artery to improve blood flow.

Almost 15 percent of patients who received stents had a stroke or died within 30 days of enrolling in the study, compared with just under 6 percent of patients in the medical therapy group. The stark difference between the groups persisted almost a year, by which time about 21 percent of patients who had received stents had had negative effects, compared with 12 percent in the medical group.

The researchers initially thought that patients who received stents would have fared better, given the successful use of similar procedures in clinical practice at the Shands at UF Stroke Program and other medical centers.

But the striking difference between the two patient groups prompted the study’s independent safety monitoring body to call off new recruitment. The researchers will, however, continue to monitor previously enrolled patients for the next two years.

It’s not unusual for surgical patients to have more complications at first, the researchers said. That’s because the invasiveness of surgery poses an inherent risk regardless of the illness being treated.

“The real question is, is there a benefit to patients over the long term,” said study co-author and co-principal investigator Hoh, who is an associate professor of radiology and neuroscience in the UF College of Medicine. “If you think about it, when people are concerned about stroke, it’s not just their first month that matters, so we’re waiting to see what the longer-term results will be.”

Over time, improvement of stent design and honing of surgical techniques could help improve outcomes for patients.

“This is certainly not the final say on managing this disease,” Waters said. “This is another piece of the puzzle that helps to guide our hand.”

Tomorrow, NASA Heads Back to the Moon, to Uncover Its Origins and to Inspire A New Generation

The GRAIL mission launches Thursday at 8:37 ET

By Rebecca Boyle

NASA's Grail Mission Twin spacecraft will orbit in tandem, measuring tiny changes in the distance between them to map the moon's gravitational field. NASA/JPL

NASA is going back to the moon once again, sending a pair of spacecraft on a quest to learn the origins of our closest companion by studying its interior and its gravitational field. But beyond new lunar science, the Gravity Recovery and Interior Laboratory, GRAIL, will also help cement NASA’s legacy of lunar exploration in the public imagination.

GRAIL A and its twin GRAIL B are set to launch Thursday morning aboard a Delta II rocket from Cape Canaveral Air Force Station. The launch window opens at 8:37 a.m. EDT, although weather looks pretty iffy for the next couple days, according to NASA. Once they arrive at the moon, the two washing machine-sized probes will fly in formation, with instruments sensitive enough to detect a hair’s breadth separation. Along with those gravity-mapping instruments, GRAIL will carry something called MoonKAM — “Moon Knowledge Acquired by Middle school students.”

Logging in from schools around the country, students will be able to virtually coast a few miles above the surface of the moon, scanning the pallid dirt for craters or perhaps an open plain that might someday make a nice lunar homestead. Students can select target areas by studying topographic maps on the MoonKAM website, and send them to NASA’s MoonKAM operations center. The images will be fairly high-resolution, but they won’t approach the abilities of the Lunar Reconnaissance Orbiter, which took the snapshots we saw this week of Apollo landing sites. But that’s not the point, said Maria Zuber, a professor of geophysics at MIT and the mission’s lead investigator.

“If a student takes an image of the surface, it’s really a transformative experience. You can bet that a smart kid will take the time to sit down and figure out how to use this software,” she said in an interview.

Each spacecraft will carry a digital camera setup with four camera heads, one pointed ahead, two pointed below and one pointed behind the spacecraft’s trajectory. They can capture video and still images up to 30 fps, and downlink them to the project’s control center at the University of California-San Diego. The program is a partnership with Sally Ride Science, a company founded by Ride, the first American woman in space.

Zuber and the other mission scientists, many of whom have kids and grandkids, hope the moon images will inspire a new generation of lunar scientists — who will understand, as they have, that the history of the moon is crucial for understanding the history of Earth.

With its perennially unchanging mountains and craters, the moon is a good proxy for the early Earth, Zuber said. Understanding how it formed could shed some light on the geologic processes behind Earth’s formation, and that of the other terrestrial planets. Just last month, researchers from the University of California-Santa Cruz said the moon may have once had asmaller sibling that it absorbed after a collision. Grail will shed some light on this question, as well as explain whether the moon has a molten core, which will provide some more information about how it coalesced.

Zuber said Grail will solve a few pieces of the larger lunar puzzle.

“If you think about your family and friends and the people you know best, if you just see what they’re like on the outside, you don’t really know them,” she said. “If you really want to know them, you want to understand what’s inside of them, and that tells you what they’re all about.”

Grail Launch Preparations: Lockheed Martin technicians verify that NASA's Gravity Recovery and Interior Laboratory-A (GRAIL-A) lunar probe is in position and ready to be secured to the spacecraft adapter ring. GRAIL-B is secured to the ring, at left.  NASA/Jim Grossmann

Grail has several unique characteristics that will help it pull this off. The spacecraft are based on a classified military satellite called XSS-11, built to demonstrate satellite rendezvous maneuvers, which helped mission planners design a system that could work well in tandem. Its avionics are modeled after the Mars Reconnaissance Orbiter, a successful mapping mission that is still sending back data. Previous gravity mapping missions, including the Gravity Recovery And Climate Experiment, also helped inform some of the project's goals, Zuber said.

Grail’s instruments are sensitive enough to measure changes of a few tenths of a micron every second, infinitesimally small differences that result from changing topographic features. But such small differences can also be caused by other phenomena, like solar wind and fuel sloshing around in the spacecraft’s tanks, for instance. Grail scientists had to account for that, too, so they are sending Grail A and B on a lengthy, circuitous course so they burn as much fuel as possible before entering orbit.

The probes will arrive at the moon as 2012 dawns, with one arriving Dec. 31 and one arriving Jan. 1. They will spend about two months synchronizing their orbits, and once everything is in alignment, the probes will spend three months making their gravity measurements. The whole mission will be done by next June, Zuber said. The spacecraft will crash into the lunar surface shortly thereafter — but not before sending photos back to schoolchildren.

Although the main mission is to map the moon’s gravity field, Grail will accomplish much more than that, Zuber said.

“It’s very hard to get a gravity mission funded. You definitely have to have the big picture in mind,” Zuber said. And for NASA, that can mean much more than just science.