http://www.npr.org/templates/story/story.php?storyId=102306350
by Joseph Shapiro
Morning Edition, March 25, 2009 · Children who have had multiple surgeries under general anesthesia by the age of 4 may be at a higher risk of developing learning disabilities, according to a new study by scientists at the Mayo Clinic in Rochester, Minn.
Dr. Robert Wilder, a Mayo Clinic anesthesiologist, says his study was motivated by recent research on baby rats and other young animals. Those studies, conducted in the last several years, show that exposure to anesthesia at a very young age can kill off brain cells. But results in rodents don't necessarily translate to humans.
"The initial reaction of the pediatric anesthesia community was, 'This must be wrong, we've been giving anesthetics to kids for years and we don't see a big problem,''' Wilder says. He, too, was skeptical.
The Mayo Clinic sits in Olmsted County. Both the research clinic and the county have kept precise records on the health care and hospitalization of its residents. Wilder sorted through the records of more than 5,000 children. About 600 of them had one or more surgeries with a general anesthesia, a class of drugs that enters the blood stream, reaches the brain and leaves a patient in a state of unconsciousness. Local anesthesia (like what's used by dentists when filling a cavity) and regional anesthesia (like an epidural that's common during childbirth) numb just a part of the body, but don't cause the patient to lose consciousness.
The surgeries ranged from those for serious problems, like open heart surgery, to more routine ones, like putting in ear tubes or removing adenoids and tonsils. Most of the kids in the study — about 80 percent — had surgeries for the small and common problems.
Wilder found that children who had undergone a single operation with a general anesthetic by the time they turned 4 were no more likely than other children to develop a learning disability.
But kids who had had two surgeries were one and a half times more at risk. And for children who had undergone three operations, the risk went up to two and a half times. Of the kids in Wilder's study who had had three or more operations, 50 percent of them later developed a learning disability.
Wilder speculates that anesthesia could cause learning problems in young children because it travels to the brain at a time when the brain is developing rapidly.
"If you're exposed to these drugs at just the right time in your life," he says, "you have a lot more cell death than you otherwise would — and some of that is in the hippocampus, which is part of the brain that is involved in learning new things and it, therefore, does not work as well throughout the rest of your life."
That makes sense to Amanda Rathbun, who lives outside Salt Lake City.
"I always thought that things like this ran in families, like if your dad has brown eyes, then you're more likely to have brown eyes. But there's not a history of this in our family," she says.
Rathbun has three very smart kids. Her 11-year-old daughter has no learning disabilities. But another daughter, who's 8, and her son, who's 13, have both been diagnosed with attention deficit disorder. Both kids had several surgeries soon after birth.
In addition, the son has struggled to write legibly. Fine motor skills are a problem for him, and Rathbun wonders if he could have gotten more attention for that sooner.
"If general anesthesia early in life can really cause these sorts of problems," she says, "I think it would be good to know that, because maybe we could start more early intervention services for these kids and maybe prevent some of these later problems."
The new research is published in the current issue of Anesthesiology, the journal of the American Society of Anesthesiologists. The co-authors write that more studies are needed to be certain it's the anesthesia that's causing the problem. It might be the illness that requires the surgery — although the researchers took the sickest children out of the study.
Wilder says parents shouldn't avoid surgery when kids younger than 4 need it.
"My advice is that if their child needs a surgical or diagnostic procedure that requires an anesthetic, then they should go ahead and have that surgical or diagnostic procedure with the anesthetic," he says.
Dr. Piyush Patel, who wrote an accompanying editorial in the same journal, agrees. He adds that parents can, however, ask their doctor if it's better to postpone a surgery until a child is older.
"Based on these data, the parents of children have to be comfortable that the surgery is absolutely needed and they have to balance the risk of waiting for the surgery to be done versus the complication that may arise," says Patel, a professor of anesthesiology at the University of California, San Diego. "This is a decision that is best made by the surgeon and the anesthesiologist."
Wilder's study, and others, have created a sense of urgency to answer questions about the effects of anesthesia on the brain development of infants and young children. Earlier this month, the federal Food and Drug Administration announced a collaboration with Mayo and other clinics to support further research.
Thursday, April 30, 2009
Wednesday, April 29, 2009
Key Gene Linked to High Blood Pressure Discovered
Tuesday , December 30, 2008
A gene that affects how the kidneys process salt may help determine a person's risk of high blood pressure, a discovery that could lead to better ways to treat the condition, researchers said on Monday.
People with a common variant of the gene STK39 tend to have higher blood pressure levels and are more likely to develop full-blown high blood pressure, also called hypertension, University of Maryland School of Medicine researchers found.
They identified the gene's role in high blood pressure susceptibility by analyzing the genes of 542 people in the insular Old Order Amish community in Lancaster County, Pennsylvania.
The researchers confirmed the findings by looking at the genes of another group of Amish people as well as four other groups of white people in the United States and Europe.
About 20 percent of the people studied had either one or two copies of this particular variant, the researchers said.
The gene produces a protein involved in regulating the way the kidneys process salt in the body — a key factor in determining blood pressure, the researchers said.
Yen-Pei Christy Chang, who led the study appearing in the journal Proceedings of the National Academy of Sciences, said the findings could lead to the development of new high blood pressure drugs targeting the activity of STK39.
"What we hope is that by understanding STK39 we can use that information for personalized medicine, so we can actually predict which hypertensive patients should be on what class of medication and know that they will respond well and have minimal risk for side effects," Chang said in a telephone interview.
People with high blood pressure are more likely to develop heart attacks, heart failure, strokes and kidney disease.
While STK39 may play a pivotal role in some people, Chang said numerous other genes also may be involved. Many factors are involved in high blood pressure such as being overweight, lack of exercise, smoking and too much salt in the diet.
Several different types of medications are used to treat high blood pressure, including diuretics, beta blockers, ACE inhibitors, calcium channel blockers and others. Their effectiveness varies depending on the person, and doctors have a hard time knowing which is best for a particular patient.
Chang said the researchers want to determine how people with different versions of this gene respond to the various drugs and to lifestyle interventions such as cutting the amount of salt in the diet.
The Lancaster Amish are seen as ideal for genetic research because they are a genetically homogenous people whose ancestry can be traced to a small group who arrived from Europe in the 1700s. In addition to genetic similarity, they also maintain similar lifestyles in their close-knit rural communities.
© Associated Press. All rights reserved.
This material may not be published, broadcast, rewritten, or redistributed.
Copyright 2009 FOX News Network, LLC. All rights reserved.
All market data delayed 20 minutes.
A gene that affects how the kidneys process salt may help determine a person's risk of high blood pressure, a discovery that could lead to better ways to treat the condition, researchers said on Monday.
People with a common variant of the gene STK39 tend to have higher blood pressure levels and are more likely to develop full-blown high blood pressure, also called hypertension, University of Maryland School of Medicine researchers found.
They identified the gene's role in high blood pressure susceptibility by analyzing the genes of 542 people in the insular Old Order Amish community in Lancaster County, Pennsylvania.
The researchers confirmed the findings by looking at the genes of another group of Amish people as well as four other groups of white people in the United States and Europe.
About 20 percent of the people studied had either one or two copies of this particular variant, the researchers said.
The gene produces a protein involved in regulating the way the kidneys process salt in the body — a key factor in determining blood pressure, the researchers said.
Yen-Pei Christy Chang, who led the study appearing in the journal Proceedings of the National Academy of Sciences, said the findings could lead to the development of new high blood pressure drugs targeting the activity of STK39.
"What we hope is that by understanding STK39 we can use that information for personalized medicine, so we can actually predict which hypertensive patients should be on what class of medication and know that they will respond well and have minimal risk for side effects," Chang said in a telephone interview.
People with high blood pressure are more likely to develop heart attacks, heart failure, strokes and kidney disease.
While STK39 may play a pivotal role in some people, Chang said numerous other genes also may be involved. Many factors are involved in high blood pressure such as being overweight, lack of exercise, smoking and too much salt in the diet.
Several different types of medications are used to treat high blood pressure, including diuretics, beta blockers, ACE inhibitors, calcium channel blockers and others. Their effectiveness varies depending on the person, and doctors have a hard time knowing which is best for a particular patient.
Chang said the researchers want to determine how people with different versions of this gene respond to the various drugs and to lifestyle interventions such as cutting the amount of salt in the diet.
The Lancaster Amish are seen as ideal for genetic research because they are a genetically homogenous people whose ancestry can be traced to a small group who arrived from Europe in the 1700s. In addition to genetic similarity, they also maintain similar lifestyles in their close-knit rural communities.
© Associated Press. All rights reserved.
This material may not be published, broadcast, rewritten, or redistributed.
Copyright 2009 FOX News Network, LLC. All rights reserved.
All market data delayed 20 minutes.
Professor Hiromitsu Nakauchi uses induced pluripotent stem to grow kidneys in genetically modified mouse
NEWS.com.auMarch 10, 2009 06:37am
Professor Hiromitsu Nakauchi uses induced pluripotent stem
to grow kidneys in genetically modified mouse
Breaking News
SCIENTISTS have successfully used implanted cells to create kidneys inside a mouse whose
parents were genetically engineered so their offspring would not be born with the organs.
The team, headed by Professor Hiromitsu Nakauchi of Tokyo University's Institute of Medical
Science, extracted a fertilised egg obtained through the normal mating of the genetically modified
parents.
The embryo was then implanted with induced pluripotent stem, or iPS, cells from a mouse with
kidneys and then transplanted into the womb of a surrogate mother.
The baby mouse was born with kidneys and it is believed its bladder inflated and it produced urine as
normal, MCT news agency reported
Implanted iPS cells are thought to have compensated for the kidneys the mouse should have been
born without.
The team now plans to use the research to create internal organs of monkeys inside pigs.
"If we become able in the future to create human kidneys inside pigs, we'll be able to solve the
problem of a lack of organs for transplant surgery," Prof Nakauchi told MCT.
Professor Hiromitsu Nakauchi uses induced pluripotent stem
to grow kidneys in genetically modified mouse
Breaking News
SCIENTISTS have successfully used implanted cells to create kidneys inside a mouse whose
parents were genetically engineered so their offspring would not be born with the organs.
The team, headed by Professor Hiromitsu Nakauchi of Tokyo University's Institute of Medical
Science, extracted a fertilised egg obtained through the normal mating of the genetically modified
parents.
The embryo was then implanted with induced pluripotent stem, or iPS, cells from a mouse with
kidneys and then transplanted into the womb of a surrogate mother.
The baby mouse was born with kidneys and it is believed its bladder inflated and it produced urine as
normal, MCT news agency reported
Implanted iPS cells are thought to have compensated for the kidneys the mouse should have been
born without.
The team now plans to use the research to create internal organs of monkeys inside pigs.
"If we become able in the future to create human kidneys inside pigs, we'll be able to solve the
problem of a lack of organs for transplant surgery," Prof Nakauchi told MCT.
Human kidneys grown in mice raise transplant hopes
December 23, 2002
Human kidneys grown in mice raise transplant hopes
By Steve Connor Science Editor
Scientists grown entire kidneys in laboratory mice using human stem cells in a development that raises the prospect of growing full-sized human organs in pigs – a breakthrough that would alleviate the worldwide shortage of kidneys for transplant operations.
Scientists grown entire kidneys in laboratory mice using human stem cells in a development that raises the prospect of growing full-sized human organs in pigs – a breakthrough that would alleviate the worldwide shortage of kidneys for transplant operations.
An Israeli team led by Professor Yair Reisner of the Weizmann Institute of Science in Rehovot grew miniature human kidneys inside the body cavities of mice in which human kidney stem cells had been transplanted. The kidneys were fully functional and produced urine.
The scientists were also able to produce pig kidneys with the same technique although in both cases the kidneys were the size of the normal mouse organ. The scientists hope now to attempt to grow human kidneys inside pigs to produce organs of a comparable size to those for human transplants.
Alternatively, they might be able to grow functioning pig kidneys inside human patients using pig foetal tissue, although this would require more careful ethical consideration because of the possibility of transferring pig viruses to people.
The study, published in the journal Nature Medicine, pinpointed the ideal time during embryonic development in which the stem cells had the best chance of forming well-functioning kidneys with minimal risk of immune rejection.
Their findings suggest that tissue seven to eight weeks old in humans and four-week-old pig tissue offers the best opportunity for transplantation. If taken earlier, the tissue could include non-kidney structures such as bone, cartilage and muscle. If taken later, then the risk of rejection by the immune system is substantial.
The work is part of a series of studies on growing entire organs using stem cells. In 1998, Marc Hammerman of Washington University in St Louis announced he had managed to grow miniature rat kidneys inside the body cavities of mice.
Professor Reisner's team also studied how the human immune system might respond to a kidney grown from human stem cells inside an animal. The scientists injected human lymphocytes – the "killer cells" of the immune system – into mice that lacked an immune system of their own.
"The findings were encouraging: as long as the kidney precursors were transplanted within the right time range, the lymphocytes did not attack the new pig or human kidneys – despite the fact that lymphocytes and kidney precursors originated from different donors," a spokesman for the Weizmann Institute said.
This suggests that such organs may not be rejected so readily if they were ever used in transplant medicine.
The team said the research was in a pre-clinical study stage, but that if all went well, a treatment could follow within a few years.
In SeptemberAmerican researchers said they had managed to grow teeth in rats, which suggested the existence of dental stem cells, and there was no reason why the technique used in rodents would not work in humans.
The shortage of kidneys for transplants is getting worse each year, according to the UK Transplant Authority. There are about 1,600 kidney transplants each year, with more than 5,000 people on the waiting list at any one time.
Human kidneys grown in mice raise transplant hopes
By Steve Connor Science Editor
Scientists grown entire kidneys in laboratory mice using human stem cells in a development that raises the prospect of growing full-sized human organs in pigs – a breakthrough that would alleviate the worldwide shortage of kidneys for transplant operations.
Scientists grown entire kidneys in laboratory mice using human stem cells in a development that raises the prospect of growing full-sized human organs in pigs – a breakthrough that would alleviate the worldwide shortage of kidneys for transplant operations.
An Israeli team led by Professor Yair Reisner of the Weizmann Institute of Science in Rehovot grew miniature human kidneys inside the body cavities of mice in which human kidney stem cells had been transplanted. The kidneys were fully functional and produced urine.
The scientists were also able to produce pig kidneys with the same technique although in both cases the kidneys were the size of the normal mouse organ. The scientists hope now to attempt to grow human kidneys inside pigs to produce organs of a comparable size to those for human transplants.
Alternatively, they might be able to grow functioning pig kidneys inside human patients using pig foetal tissue, although this would require more careful ethical consideration because of the possibility of transferring pig viruses to people.
The study, published in the journal Nature Medicine, pinpointed the ideal time during embryonic development in which the stem cells had the best chance of forming well-functioning kidneys with minimal risk of immune rejection.
Their findings suggest that tissue seven to eight weeks old in humans and four-week-old pig tissue offers the best opportunity for transplantation. If taken earlier, the tissue could include non-kidney structures such as bone, cartilage and muscle. If taken later, then the risk of rejection by the immune system is substantial.
The work is part of a series of studies on growing entire organs using stem cells. In 1998, Marc Hammerman of Washington University in St Louis announced he had managed to grow miniature rat kidneys inside the body cavities of mice.
Professor Reisner's team also studied how the human immune system might respond to a kidney grown from human stem cells inside an animal. The scientists injected human lymphocytes – the "killer cells" of the immune system – into mice that lacked an immune system of their own.
"The findings were encouraging: as long as the kidney precursors were transplanted within the right time range, the lymphocytes did not attack the new pig or human kidneys – despite the fact that lymphocytes and kidney precursors originated from different donors," a spokesman for the Weizmann Institute said.
This suggests that such organs may not be rejected so readily if they were ever used in transplant medicine.
The team said the research was in a pre-clinical study stage, but that if all went well, a treatment could follow within a few years.
In SeptemberAmerican researchers said they had managed to grow teeth in rats, which suggested the existence of dental stem cells, and there was no reason why the technique used in rodents would not work in humans.
The shortage of kidneys for transplants is getting worse each year, according to the UK Transplant Authority. There are about 1,600 kidney transplants each year, with more than 5,000 people on the waiting list at any one time.
How Morphine Can Be Given More Effectively Without Having To Increase Dosages
ScienceDaily (Apr. 28, 2009) — Researchers at the Hebrew University of Jerusalem have found a way to maintain the pain-killing qualities of morphine over an extended period of time, thus providing a solution for the problem of having to administer increasing dosages of the drug in order to retain its effectiveness.
One of the limitations in long-term use of morphine for pain relief is the rapid development of tolerance. The effectiveness of morphine declines quickly, and one must increase the dosage in order to preserve effective pain relief. However, the increased dosage also increases negative side effects.
The Hebrew University researchers, Prof. Yehuda Shavit and his graduate student Gilly Wolf of the Psychology Department, found that administration of morphine causes a substance called interleukin-1 to be released.
Under normal circumstances, interleukin-1 plays an important role in survival. In case of tissue damage, nerve injury, or inflammatory reaction, inteleukin-1 is released and sets off a process which increases the sensitivity to pain in the injured area. This pain serves as a warning signal, telling the body that there is a problem that should be attended to. In case of chronic pain, morphine is still the drug of choice for pain relief.
However, since prolonged administration of morphine raises the level of interleukin-1, thereby enhancing pain sensitivity, the effectiveness of morphine as a pain killer is steadily reduced, requiring greater dosages with accompanying negative side effects.
The Hebrew University researchers were able to show in animal experiments that administering morphine together with another drug that blocks the activity of interleukin-1 provides more effective pain relief over the long term without having to increase the dosage.
Shavit, who is the Leon and Clara Sznajderman Professor of Psychology at the Hebrew University and whose specialty is psychoneuroimmunology, expressed hope that this research will make it possible for clinicians to make use of morphine, together with substances that block interluekin-1, in order to bring about better pain relief with lower dosages and with minimized side effects. The research will be presented at a conference on pain research on May 3 on the Mount Scopus campus of the university. The conference is open to journalists and to people in the field.
One of the limitations in long-term use of morphine for pain relief is the rapid development of tolerance. The effectiveness of morphine declines quickly, and one must increase the dosage in order to preserve effective pain relief. However, the increased dosage also increases negative side effects.
The Hebrew University researchers, Prof. Yehuda Shavit and his graduate student Gilly Wolf of the Psychology Department, found that administration of morphine causes a substance called interleukin-1 to be released.
Under normal circumstances, interleukin-1 plays an important role in survival. In case of tissue damage, nerve injury, or inflammatory reaction, inteleukin-1 is released and sets off a process which increases the sensitivity to pain in the injured area. This pain serves as a warning signal, telling the body that there is a problem that should be attended to. In case of chronic pain, morphine is still the drug of choice for pain relief.
However, since prolonged administration of morphine raises the level of interleukin-1, thereby enhancing pain sensitivity, the effectiveness of morphine as a pain killer is steadily reduced, requiring greater dosages with accompanying negative side effects.
The Hebrew University researchers were able to show in animal experiments that administering morphine together with another drug that blocks the activity of interleukin-1 provides more effective pain relief over the long term without having to increase the dosage.
Shavit, who is the Leon and Clara Sznajderman Professor of Psychology at the Hebrew University and whose specialty is psychoneuroimmunology, expressed hope that this research will make it possible for clinicians to make use of morphine, together with substances that block interluekin-1, in order to bring about better pain relief with lower dosages and with minimized side effects. The research will be presented at a conference on pain research on May 3 on the Mount Scopus campus of the university. The conference is open to journalists and to people in the field.
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