By Elizabeth Svoboda
www.wired.com

Stem cells embedded in futuristic materials may heal decades-old spinal cord injuries and rescue patients from paralysis, if recent experiments in rodents can be replicated in humans.

Stem cells have cured many rats of spinal cord injuries, but the treatment has yet to benefit humans. When it does, most scientists say the first treatments will benefit only the newly injured.

But Pavla Jendelova, a biologist at the Institute of Experimental Medicine in Prague, Czech Republic, found that adding stem cells to spinal implants made of hydrogels — jelly-like polymers consisting of latticed networks of amino acids — could build a bridge in spinal cords even with older injuries, and help patients to regain function.

“In chronic spinal cord injuries, there’s a large cavity that develops over time in the injured area,” she said. “We want to see if the hydrogels can breach this gap.”

Hydrogels resemble the soft tissue that surrounds a human spinal cord as it develops in the womb, Jendelova said. Neurons grow through pores in the material, creating a scaffold that supports delicate cells. The pores are also large enough to allow the transmission of chemical signals that orchestrate neural development.

Jendelova believes hydrogels’ physical properties, which are similar to those of Jell-O, increase the likelihood that stem cells will integrate successfully with existing spinal tissue.

“An ideal matrix for neurons would be soft, chemically inert and would have a high water content like a sponge — something that resembles the natural environment around developing neural tissue,” she said. Made of up to 99 percent water, hydrogels come closer to meeting these criteria than any other artificial material.

The Institute of Experimental Medicine team induced spinal cord lesions in 28 rats by removing small sections of the cord or compressing spinal cord tissue. They then filled the spinal cavity around the injured area with blocks of hydrogel laced with stem cells from rat bone marrow.

Four weeks later, the scientists analyzed the treated areas and found that the stem cells had successfully built new spinal cord tissue with nerve fibers that grew through the gaps in the hydrogel’s amino-acid lattice. “We observed significant growth of neural tissue into the hydrogels,” Jendelova said. “There were neurofilaments, axons and connective tissue growing into the whole area of the lesion.”

Not only did the rats show unprecedented neural regrowth, they also recovered much of the limb function they had lost when the researchers initially injured them. Jendelova presented her findings last month at the Cambridge Healthtech Institute’s molecular medicine conference in San Francisco.

“If you create a physical architecture, cells will often follow it,” said Erin Lavik, a biomedical engineer at Yale University who is developing hydrogels that can be used as matrices to build blood vessel networks. The technique could prove crucial in tissue and spinal cord repair procedures.

Scientists have also tried nanofibers as frameworks for stem cell growth, Lavik said, but because they are engineered to be strong and tough, they are less flexible and don’t readily mold to a lesion.

The nervous system is not a particularly hospitable environment for nerve regeneration to begin with, said Itzhak Fischer, a molecular neurobiologist at Drexel University who specializes in spinal cord repair. “But if you can insert a scaffold that directs neural cells exactly where you want them, you’re going to have a much better result,” Fischer said.

For several years, Fischer has been investigating which hydrogel formulations best facilitate neural tissue growth. He is currently experimenting with “permissive peptides” — protein strands attached to the gel’s surface that attract newly developing nerve fibers.

In late 2004, Fischer and his colleagues implanted hydrogels drenched with a growth-factor compound similar to that secreted by stem cells into the severed spinal cords of 24 adult rats. The rats grew new, mature neurons, which are necessary for spinal cord development.

Despite his and Jendelova’s early success, Fischer foresees future roadblocks. “It’s tricky to make stem cells compatible with the nervous system environment,” he said. Even if a hydrogel scaffold works beautifully, the body’s immune system still might reject the foreign cells.

Like Fischer, Jendelova is cautious — she estimates gel-based spinal cord repair clinical trials will begin within the next five years, but it’s too soon to predict whether the treatment will translate into humans.

“The problem with transferring results from rodents to humans is that there are so many size differences,” she said. “The hydrogels may be fine for a rat’s small spinal cord, but we can’t say whether they will work as well in a human one, which is more than 10 times thicker.” Recently, however, she conducted hydrogel experiments in five pigs with injured spinal cords. The results suggest the gel implants may scale up better than she expected.

Several other stem cell-based techniques have cured rats of paralysis, but scientists have yet to try the techniques in humans. Hans Keirstead, an assistant professor of anatomy and neurobiology at the Reeve-Irvine Research Center, is one of them. His work is funded by Geron, and the company’s chief scientific officer, Tom Okarma, said his scientists could begin human clinical trials using Keirstead’s technique in 2007 — but the first study will focus on newly injured patients.

Evan Snyder has also restored movement to previously paralyzed rats using a stem cell therapy.

Ultimately, according to Aileen Anderson, a neurobiologist at the University of California at Irvine, hydrogels could emerge as front-runners among the many stem cell-based spinal cord repair strategies being developed.

“There have certainly been experiments showing that you don’t have to have a hydrogel scaffold to achieve some spinal cord regeneration,” she said. “But they might be really useful in certain situations — especially in injuries where the spinal cord is completely cut in two, and the scaffold forms a bridge between the sections.”
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By Robert Lee Hotz, Times Staff Writer

Smart children have a different rhythm in their heads — a seesaw pattern of growth that lags years behind other young people — say government scientists who mapped the brains of hundreds of children.

Seeking a link between neural anatomy and mental ability, researchers at the National Institute of Mental Health and McGill University in Montreal discovered it where they least expected — not in sheer brain size or special structures, but in the patterns of childhood growth.

Brain development in children with the highest IQ peaked four years later than among average children, the researchers reported Wednesday in the journal Nature.

“Smart children really do develop differently, and here is the first physical evidence of that,” said UCLA neuroscientist Paul Thompson, an expert on imaging and brain development. “You’d think they’d develop faster and earlier than normal kids. The surprise is they don’t.”

Philip Shaw at the NIMH child psychiatry branch and his colleagues periodically scanned the brains of 307 healthy children from age 5 to age 19.

To monitor the living brains, they used magnetic resonance imaging, which can detect the anatomical differences between gray matter, composed of neurons and other brain cells, and white matter, composed of the nerves that connect them. They gauged intelligence by giving each child standard IQ tests.

In general, every brain blossoms from a single cell in the womb, growing at a rate of 250,000 cells a minute until, by early childhood, it has more neurons and more connections between them than the average adult brain. Unused cells and synapses then atrophy and die.

When the researchers analyzed their images, they discovered patterns of brain development that differed depending on the child’s age and IQ.

The scans revealed tell-tale waves of change that coursed through the brain’s prefrontal cortex — a thick wrinkled carpet of cells that orchestrates memory, attention, perceptual awareness, language, reason and consciousness. “The story of intelligence is in the trajectory of brain development,” Shaw said. “What differs with intelligence is the rate of these changes.”

Among average children — those with an IQ measuring 83 to 108 — the growth of the cortex peaked at age 8, while among those with high intelligence — rated with an IQ of 109 to 120 — growth peaked at age 9.

The smartest children — those with IQs measuring 121 to 145 — displayed a pattern of brain growth that peaked at age 11 or 12, the researchers said.

The anatomical scans revealed that among the most intelligent children, the cortex displayed the most prolonged period of growth and the most rapid rate of change. The cortex also was thinner in early childhood, grew thicker, then thinned more rapidly.

“There is something very dynamic about these brains,” said Judith L. Rapoport, chief of the NIMH child psychiatry branch. “What the intelligent children have is a very malleable brain.”

By the teen years, however, the cortex could be seen to be thinning in all three groups and, by adulthood, the brains could no longer be distinguished by IQ differences, said NIMH brain imaging expert Jay Giedd.

“Even though they end up at pretty much the same place, the shape of the [development] curve and the age at which they peak is very different between the three groups,” he said. “We would have missed it if we had looked at adults.”

No single brain scan could reveal a child’s IQ. The patterns only revealed themselves across a large group. The differences are measured in fractions of a millimeter of brain tissue that emerge over a decade or more.

“These are tiny changes,” Shaw said. “But in brain terms, it is a lot.”

No one knows whether such subtle developmental changes in the cortex are caused by the genes inherited from a child’s parents, by the biochemical influences of life experience, or by the interplay of both.

“It is tempting to assume that this developmental change in brain structure is determined by a person’s genes,” said psychologist Richard Passingham at the University of Oxford, who wrote a commentary accompanying the Nature paper. “But one should be wary of such a conclusion.”
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By POLLY ROSS HUGHES
Copyright 2006 Houston Chronicle Austin Bureau

If pandemic bird flu begins spreading from one human to another, millions could fall ill in the United States, but the federal government wouldn’t be able to respond everywhere at once, U.S. Secretary of Health and Human Services Michael Leavitt warned Monday.

“Any community that fails to prepare with the expectation that the federal government will come to the rescue will be tragically wrong,” Leavitt said at a Texas pandemic influenza summit hosted by the Texas Department of State Health Services.

“There is no way that a national government could respond to 5,000 locations at the same time,” he added. “This is the difference between a pandemic and any other disaster.”

So far, isolated cases of bird-to-human transmissions of a virulent form of the flu have resulted in 105 human deaths overseas. The illness has not been detected in this country, but some estimate it could arrive with migrating birds within six months.

Even then, however, the virus must mutate further before it could spread from one human to another. No one is certain whether it will mutate or how long that might take.

Leavitt and other health and government officials at the summit urged local governments, schools, businesses and individual families to begin preparing now for a potential health disaster that could well rival the 1918 Spanish flu.

“A pandemic of the same proportion as we had in 1918 would cause 90 million people in the United States to become ill,” Leavitt said. “Half, 45 million, would require serious medical attention and about 2 million would die.”

In Texas, that would translate to 7 million people becoming ill and 3.5 million needing serious medical attention, he said.

Communication is critical
About 300 representatives from business, government, education, hospitals and the military began forming plans at the pandemic influenza summit where they learned that reliable communications will be critical in dealing with the potential economic chaos that could ensue.

Up to 30 percent of the population at any time could become infected and force half of all workers to stay home, threatening food supplies and other basics critical for survival, the experts warned.

Should a pandemic occur, it would last 12-18 months and hit in waves lasting six to eight weeks each, Leavitt said. During that time the country might also be forced to cope with natural disasters or terrorist attacks.

“No one is well-prepared for a pandemic,” he said. “When it comes to a pandemic, we’re overdue and underprepared.”

Texans must grapple with ethical decisions about who gets vaccines or medical help and who doesn’t, said Texas Health Commissioner Eduardo San- chez.

“How do we continue doing the business at hand?” he asked. “If you think about even what happened with Katrina and Rita, there will be disruption at the business level, school level and community-based organization level.”

Gov. Rick Perry, noting that Texas is receiving nearly $6 million in pandemic flu preparedness funds out of $100 million distributed by the federal government, said the state began planning for such a disaster in 2004 and its strategic disaster plans envision epidemics.

Tough decisions ahead

Sanchez said every individual family also will be forced to make tough decisions about whether to stay home and care for sick family members or children barred from schools or to go to work to help provide critical infrastructure such as food, electricity and water.

“This isn’t just a bunch of hoopla,” Sanchez said, noting that if the flu mutates to spread among human beings, it could spread globally in weeks, its impact would be measured within months and no state or community would be unaffected.

“We’re overdue for a pandemic,” warned Dr. Kevin J. Soden, worldwide medical director of Texas Instruments, predicting migratory birds carrying the disease could arrive in the U.S. within six weeks.

“Most countries are not prepared for something like that, including ourselves. The risk is great and will persist. It really is a matter of when and not if,” he said.

Scientists are particularly concerned about the H5N1 strain, a virulent form of avian flu virus currently spreading through Asia and parts of Europe, infecting poultry and migratory birds.

Half of all humans infected by birds in Thailand, Vietnam, Cambodia and Indonesia since October have died.

Out of 169 known strains of avian flu, only this one is closely related to the pandemic flu of 1918 that killed 50 million to 100 million people worldwide, shut down schools and churches, resulted in mass graves and spread hysteria and panic in its wake, Soden said.

To illustrate the magnitude of the problem, Soden said the United States today has only 100,000 respirators but would need more than 1 million during a pandemic.

Emergency rooms already overwhelmed with 41 million people who are uninsured will not be able to cope with nearly one-third of the population ill at once, he said.

An intensive care staff of eight would need 80,000 gloves to carry on for six weeks, but 80 percent of all medical supplies originate overseas, he added.

“What’s going to happen if a wave hits over there first and countries are totally disrupted? What’s going to happen to our supplies,” he asked. “We don’t stockpile that.”
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By Christopher Rowland, Globe Staff

In a move that has divided physicians in Worcester, the University of Massachusetts Medical School and its clinical affiliate, UMass Memorial Medical Center, plan to drastically cut their academic relationship with rival Saint Vincent Hospital.

The decision will result in the loss next year of 20 surgical, emergency medicine, and other medical residency positions at Saint Vincent. The positions, for prospective physicians in the last stages of training, will be moved to UMass Memorial and other UMass-affiliated hospitals in Central Massachusetts.

The Saint Vincent residency slots represent a small fraction of the 453 that UMass offers, and some training for university medical students will still take place at Saint Vincent. But the end of the residency program signals a deteriorating relationship between the institutions.

UMass says it has a bigger commitment to medical training than the for-profit Saint Vincent, which is owned by Vanguard Health System Inc. of Nashville.

Saint Vincent officials say the larger UMass system is motivated by business concerns. The 350-bed Saint Vincent Hospital in downtown Worcester is the primary competition for the nonprofit UMass Memorial Medical Center, which has 767 beds spread across three city campuses.

”There certainly is an underlying agenda here regarding competition for market share in Central Massachusetts,” said Dr. Jeffrey Steinberg, Saint Vincent’s chief of surgery.

”It is a contentious atmosphere and there is a significant rift between the staffs of the two institutions because of this decision,” he said. ”We feel we have always been a very good educational partner.”

Unless Saint Vincent’s finds another academic partner, the loss of the residency positions could diminish its standing as Worcester’s alternative teaching hospital. Both UMass and Saint Vincent draw patients from throughout Central Massachusetts and as far east as the fast-growing Boston suburbs along the Interstate 495 corridor.

A spokesman for UMass Medical School and UMass Memorial, Mark Shelton, denied market competition played a role in the decision to pull the residency positions from Saint Vincent. UMass wants most of its residency positions to be under direct supervision of the university, Shelton said.

”The business of UMass Medical School is education,” he said. ”Our shareholders are the people of the Commonwealth. There is always reasonable consciousness that for-profit hospitals might not necessarily be able to place education in the same place in the hierarchy as the medical school does.”

Joseph J. Mullany, president of New England operations for Vanguard, said Saint Vincent’s administrators and physicians do place a high value on education. Vanguard officials are courting a new academic partner from among Boston’s medical schools and academic medical centers, he said. Tufts-New England Medical Center confirmed it has spoken with Vanguard officials about the possibility of a residency affiliation.

Mullany said he was told during a February meeting with UMass Memorial Medical Center chief executive John O’Brien and medical school chancellor Aaron Lazare that the residency positions would be moved.

The change will take effect in July 2007, he said, which does not give Saint Vincent’s enough time to win certification for new residency slots of its own. Mullany said he has asked Lazare to reconsider, but has not received a response.

Among those caught in the middle of the dispute are physicians like Dr. David A. Kaufman, an associate dean for medical education at the medical school and chief of the department of critical care at Saint Vincent.

At a February meeting of a UMass graduate medical education committee where the termination was discussed, Kaufman called it ”regrettable.” Thousands of UMass residents and fellows have enjoyed an excellent educational experience at Saint Vincent Hospital over three decades, he said.

According to the minutes, UMass officials cited a desire to consolidate programs at the school’s clinical sites. They also cited a reduction in residents’ workloads to a maximum of 80 hours per week from 120. With residents on duty fewer hours, the demand for the number of residents has risen, they said.

Vanguard bought Saint Vincent Hospital and the MetroWest Medical Center, with campuses in Framingham and Natick, from Tenet Healthcare Corp. for about $167 million in 2005. Saint Vincent was previously owned by OrNda HealthCorp., which was bought out by Tenet in 1997.
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The Children’s Advocacy Project, a one-stop resource, helps doctors quickly meet patients’ nonmedical needs.

By Brian Rademaekers
For The Inquirer
www.philly.com

When 18-year-old Anise Taylor’s second son was born with a pituitary condition that left him blind, she had questions about more than just his health.

How could she afford to buy his medication? Who would take care of him while she worked? And where could he go to school?

Anise’s despair is common.

Every day, families struggle with a fragmented system for health and social services that can be impossible to navigate.

But thanks to the Children’s Advocacy Project, a Web site created by Philadelphia pediatrician Daniel Taylor and Drexel faculty member Jervis Thompson, a growing number of doctors nationally can now provide people like Anise with answers to the toughest nonmedical questions in a matter of minutes.

The 18-month-old Web site, which receives up to 3,000 visits per day, has been so successful in Philadelphia that New York City and Hawaii joined the service this month.

And now people across the nation, including those in York, Pittsburgh, Rochester, N.Y., Boston, St. Louis, Atlanta, and the state of Delaware, are clamoring to participate.

“Linking up every city in the nation would be a dream come true,” Taylor said.

Developed in 2004, the Web site, www.cap4kids.org, works like an electronic phone book that provides doctors and families with an easy-to-use database of services, ranging from after-school programs to domestic-violence counseling and employment opportunities.

Leora Mogilner, a pediatrician from Mount Sinai University who is helping to build the New York site, called the database “an invaluable tool” that should change the way doctors relate to their patients.

“Doctors may be aware of these resources, but there has never been a single trusted place where all these things were at their fingertips,” she said. “This streamlines it.”

Chris Derauf, a pediatrician who leads the Hawaii effort, agreed. More than half of his patients would benefit from some type of social aid, he said.

The resource already has changed the way some doctors practice.

Danielle Casher, a pediatrician in Philadelphia’s Roxborough section, said the Web site was the first place she went for patients with nonmedical issues.

Recently, a mother learned her child had autism. Casher was able to use the site to quickly provide her with the number of a person who could help her find the right school for the child.

“Before I would have been in the morass of the Philadelphia public school system,” Casher said.

Closing the gap

Two main factors create the gap between doctors and social services: There’s little training that promotes coordination among professionals, and no pay for doctors to give social assistance, said Robert I. Field, director of the graduate program in health policy at the University of the Sciences in Philadelphia.

“People tend to do what they are paid for,” Field said. “When these types of services aren’t valued by the payment structure, it is human nature not to pay attention to them.”

Alisa Simon, health policy director at Philadelphia Citizens for Children and Youth, said that doctors who simply gave kids medical attention weren’t doing enough.

“If they’re getting their shots, but not enough food in between, we are failing them,” she said.

Calls to Simon’s group soared after its number was added to the Web site, she said.

It costs just $2,000 for a town or state to join, Drexel professor Thompson said. Each area has a designated administrator to keep the site updated.

A personal payoff

Thompson, who donates a few hours of work to the site each week, said his payoff was personal.

“Some of the services listed are services my family used when I was growing up,” said Thompson, a Bronx native who is working to connect the New York site.

To help Anise, the young mother, pediatrician Taylor was able to connect her to Social Security aid for disabled children, medical day care, and therapists who come to her home each week. He also helped find Anise a school for the blind when her son is old enough.

For Taylor, this makes his job complete.

“It breaks down the walls between physician and family,” he said. The effort “lets them know I’m on their team.”

On the Web

Here are some additional Web sites helping doctors and families:

www.kidshealth.org

This national site has resources for parents, children and teens.

It includes articles that explain illnesses and related problems and contact information for organizations that can help.

www.phillysos.org

Operated by the Philadelphia Department of Human Services, this comprehensive list of social services can be searched by keyword, agency, or type of service needed.

www.philasafesound.org

This enables you to search for area programs for children and young adults according to your address.

www.phillyhealthinfo.org

Run by the College of Physicians of Philadelphia, this site connects people of all ages to health and social services in the area.
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