Utah tests may lead to stem-cell treatment of kidney failure
By Heather May
The Salt Lake Tribune
Article Last Updated: 09/30/2008 03:14:55 PM MDT
Utah researchers are testing whether they can safely inject adult stem cells into patients to prevent and treat acute kidney failure.
Intermountain Medical Center and AlloCure, a Utah-based biotech company, have teamed up to test AlloCure's patented cells in patients who have had open-heart surgery. That kind of major operation can lead to acute kidney injury, which can be deadly.
"These cells enable an organ to defend itself against injury," said Christof Westenfelder, AlloCure's chief medical officer.
The researchers are recruiting 15 patients in what they say is the first use of adult stem cells for such kidney problems.
The cells are obtained from healthy adult donors' bone marrow. AlloCure grows and processes them in a lab, making them essentially invisible to the patient's immune system so that the patient and donor don't have to match blood or tissue types.
The cells are injected through a catheter into the bloodstream. Chemical signals lead the cells to the kidney, where, according to AlloCure, animal studies have shown they promote the survival and growth of kidney cells so that the organ can repair itself.
After that work is done, Westenfelder said, the stem cells enter the circulatory system, where they self-destruct. That's important so that the cells don't create bone, fat or muscle - which is what bone marrow stem cells do - in the wrong place.
The clinical trial is in the first of three phases, which means researchers are studying whether or not the cells are safe in humans. If the study proceeds, researchers will determine if the stem cells protect and heal kidneys.
Two Utah patients have been injected so far with "no obvious complications," said John Doty, a cardiovascular surgeon at IMC and the study's principal investigator. AlloCure is funding the study.
Possible side effects include complications with the catheter and blood vessel blockages from the stem cells.
The researchers said doctors need a better way to treat kidney damage after heart surgery. For the serious cases, patients must go on dialysis. But half of those dialysis patients will die before leaving the hospital, Doty said.
hmay@sltrib.com
Friday, October 24, 2008
Ultrasound cuff to stop internal bleeding on battlefield
October 22, 2008 6:00 AM PDT
Ultrasound cuff to stop internal bleeding on battlefield
Posted by Mark Rutherford Post a comment
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(Credit: DARPA)
Internal bleeding can cause irreversible haemorrhagic shock within 30 seconds or progressive shock within eight hours, either way, it's not good and the military wants a portable, noninvasive way to detect and stop it right on the battlefield.
To that end, the Defense Advance Research Projects Agency (DARPA) has contracted with Siemens Healthcare, the University of Washington's Centre for Industrial and Medical Ultrasound and Texas A&M to develop something called the Deep Bleeder Acoustic Coagulation cuff (DBAC). The cuff is a semi-automated, ultrasound device designed to cut blood loss and shock resulting from combat limb injuries, one that can be operated by any GI with minimal training.
As it stands now, a wounded soldier can quickly lose 25 percent of blood volume while waiting to be evacuated. This can lead to progressive shock and death. On the spot treatment with the cuff would curtail these needless combat deaths and amputations, according to the military.
A medic applies the cuff to the injured limb, the DBAC automatically locates the bleeding and triggers a dose of high-intensity, focused ultrasound toward it, this prompts quick coagulation and an end to the bleeding.
The system uses doppler-based "automated bleed detection algorithms," according to DARPA. The software used is based on "unique spectral and power Doppler bleeder signatures that, when coupled to volumetric data, allows for automated bleed detection and localization."(PDF)
Blood mimicking fluids and heat resistant, tissue mimicking phantoms were custom created to allow DBAC testing on a full-sized leg mockup. DARPA hopes to be able to have a prototype in 18 months.
Mark Rutherford is a West Coast-based freelance writer. He is a member of the CNET Blog Network, and is not an employee of CNET. Email him at markr@milapp.com. Disclosure.
Combined kidney and bone marrow transplantation allows patients to discontinue anti-rejection drugs
Combined kidney and bone marrow transplantation allows patients to discontinue anti-rejection drugs
Researcher reports progress of clinical trial to International Transplantation Society
AUGUST 26, 2002
Megan Sykes, head of the bone marrow transplantation section of the Massachusetts Transplantation Biology Research Center and professor of surgery at Harvard Medical School, recently described how infusing kidney transplant recipients with bone marrow from their donors immediately after the transplant surgery induced a state of mixed chimerism, a blending of donor and recipient immune systems. All of the patients Sykes described had developed kidney failure as a result of multiple myeloma, a cancer of the bone marrow. Traditionally, such patients had no good treatment options. They were not eligible for kidney transplantation because of their cancer, and the kidney failure made them unable to tolerate the toxic aspects of standard bone marrow transplantation, which has been used for some myeloma patients. For many years Sykes and her colleagues at MGH -- along with collaborators at BioTransplant Inc. of Charlestown, Mass. -- have been studying mixed chimerism and its application for both treatment of blood-cell cancers and for inducing tolerance, a state in which an organ recipient's immune system no longer recognizes the donor's tissues as foreign.
Contributed by Massachusetts General Hospital
http://harvardscience.harvard.edu/medicine-health/articles/combined-kidney-and-bone-marrow-transplantation-allows-patients-discontinue
Researcher reports progress of clinical trial to International Transplantation Society
AUGUST 26, 2002
Megan Sykes, head of the bone marrow transplantation section of the Massachusetts Transplantation Biology Research Center and professor of surgery at Harvard Medical School, recently described how infusing kidney transplant recipients with bone marrow from their donors immediately after the transplant surgery induced a state of mixed chimerism, a blending of donor and recipient immune systems. All of the patients Sykes described had developed kidney failure as a result of multiple myeloma, a cancer of the bone marrow. Traditionally, such patients had no good treatment options. They were not eligible for kidney transplantation because of their cancer, and the kidney failure made them unable to tolerate the toxic aspects of standard bone marrow transplantation, which has been used for some myeloma patients. For many years Sykes and her colleagues at MGH -- along with collaborators at BioTransplant Inc. of Charlestown, Mass. -- have been studying mixed chimerism and its application for both treatment of blood-cell cancers and for inducing tolerance, a state in which an organ recipient's immune system no longer recognizes the donor's tissues as foreign.
Contributed by Massachusetts General Hospital
http://harvardscience.harvard.edu/medicine-health/articles/combined-kidney-and-bone-marrow-transplantation-allows-patients-discontinue
Bone-marrow-derived stem cells can reverse genetic kidney disease
Bone-marrow-derived stem cells can reverse genetic kidney disease
APRIL 24, 2006
The discovery that bone-marrow derived stem cells can regenerate damaged renal cells in an animal model of Alport syndrome provides a potential new strategy for managing this inherited kidney disease and offers the first example of how stem cells may be useful in repairing basement membrane matrix defects and restoring organ function.
Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the findings are described in the Proceedings of the National Academy of Sciences (PNAS), which appeared on-line the week of April 24, 2006.
Symptoms of Alport syndrome, the second-most common genetic cause of kidney failure, usually appear in children, affecting the kidneys' filtration system and typically leading to end-stage renal disease in the patient's teens, 20s or 30s. The disease additionally causes deafness in some patients.
"This is one of 31 human diseases that occur because of genetic defects in the body's extracellular matrix and basement membrane proteins," explains the study's senior author, Raghu Kalluri, PhD, chief of the division of matrix biology at BIDMC and associate professor of medicine at Harvard Medical School.
Contributed by Beth Israel Deaconess Medical Center
http://harvardscience.harvard.edu/medicine-health/articles/bone-marrow-derived-stem-cells-can-reverse-genetic-kidney-disease
The Stink in Farts Controls Blood Pressure
The Stink in Farts Controls Blood Pressure
By Amelia Tomas, LiveScience Staff
posted: 23 October 2008 02:52 pm ET
A smelly rotten-egg gas in farts controls blood pressure in mice, a new study finds.
The unpleasant aroma of the gas, called hydrogen sulfide (H2S), can be a little too familiar, as it is expelled by bacteria living in the human colon and eventually makes its way, well, out.
The new research found that cells lining mice’s blood vessels naturally make the gas and this action can help keep the rodents’ blood pressure low by relaxing the blood vessels to prevent hypertension (high blood pressure). This gas is “no doubt” produced in cells lining human blood vessels too, the researchers said.
“Now that we know hydrogen sulfide’s role in regulating blood pressure, it may be possible to design drug therapies that enhance its formation as an alternative to the current methods of treatment for hypertension,” said Johns Hopkins neuroscientist Solomon H. Snyder, M.D., a co-author of the study detailed in the Oct. 24th issue of the journal Science.
Snyder and his colleagues compared normal mice to mice that were missing a gene for an enzyme known as CSE, long suspected as being responsible for making hydrogen sulfide. As they measured hydrogen sulfide levels taken from tissues of the CSE-deficient mice, the scientists found that the gas was depleted in the cardiovascular systems of the altered mice. By contrast, normal mice had higher levels of the gas, thereby showing that hydrogen sulfide is naturally made by mammalian tissues using CSE.
Next, the mice were subjected to higher blood pressures comparable to serious hypertension in humans. Scientists had them respond to a chemical called methacholine that relaxes normal blood vessels. The blood vessels of the CSE-lacking mice hardly relaxed, indicating that hydrogen sulfide is a huge contender for regulating blood pressure.
Hydrogen sulfide is the most recently discovered member of a family of gasotransmitters, small molecules inside our bodies with important physiological functions.
This study is the first to reveal that the CSE enzyme that triggers hydrogen sulfide is activated itself in the same way as other enzymes when they trigger their respective gasotransmitter, such as a nitric oxide-forming enzyme that also regulates blood pressure, Dr. Snyder said.
Because gasotransmitters are common in mammals all over the evolutionary tree, these findings on the importance of hydrogen sulfide are thought to have broad applications to human diseases, such as diabetes and neurodegenerative diseases.
The research was supported by grants from the U.S. Public Health Service and the Canadian Institutes of Health Research as well as a Research Scientist Award.
By Amelia Tomas, LiveScience Staff
posted: 23 October 2008 02:52 pm ET
A smelly rotten-egg gas in farts controls blood pressure in mice, a new study finds.
The unpleasant aroma of the gas, called hydrogen sulfide (H2S), can be a little too familiar, as it is expelled by bacteria living in the human colon and eventually makes its way, well, out.
The new research found that cells lining mice’s blood vessels naturally make the gas and this action can help keep the rodents’ blood pressure low by relaxing the blood vessels to prevent hypertension (high blood pressure). This gas is “no doubt” produced in cells lining human blood vessels too, the researchers said.
“Now that we know hydrogen sulfide’s role in regulating blood pressure, it may be possible to design drug therapies that enhance its formation as an alternative to the current methods of treatment for hypertension,” said Johns Hopkins neuroscientist Solomon H. Snyder, M.D., a co-author of the study detailed in the Oct. 24th issue of the journal Science.
Snyder and his colleagues compared normal mice to mice that were missing a gene for an enzyme known as CSE, long suspected as being responsible for making hydrogen sulfide. As they measured hydrogen sulfide levels taken from tissues of the CSE-deficient mice, the scientists found that the gas was depleted in the cardiovascular systems of the altered mice. By contrast, normal mice had higher levels of the gas, thereby showing that hydrogen sulfide is naturally made by mammalian tissues using CSE.
Next, the mice were subjected to higher blood pressures comparable to serious hypertension in humans. Scientists had them respond to a chemical called methacholine that relaxes normal blood vessels. The blood vessels of the CSE-lacking mice hardly relaxed, indicating that hydrogen sulfide is a huge contender for regulating blood pressure.
Hydrogen sulfide is the most recently discovered member of a family of gasotransmitters, small molecules inside our bodies with important physiological functions.
This study is the first to reveal that the CSE enzyme that triggers hydrogen sulfide is activated itself in the same way as other enzymes when they trigger their respective gasotransmitter, such as a nitric oxide-forming enzyme that also regulates blood pressure, Dr. Snyder said.
Because gasotransmitters are common in mammals all over the evolutionary tree, these findings on the importance of hydrogen sulfide are thought to have broad applications to human diseases, such as diabetes and neurodegenerative diseases.
The research was supported by grants from the U.S. Public Health Service and the Canadian Institutes of Health Research as well as a Research Scientist Award.
Stem Cell Transplant Succeeds in Curing Kidney Failure in Rats
Stem Cell Transplant Succeeds in Curing Kidney Failure in Rats
Mainichi Daily News
21 June 2005
A research team led by the University of Tokyo has succeeded in curing renal failure in rats by transplanting somatic stem cells of kidneys from healthy rats.
The team announced the results of their research in the June 20 issue of a U.S. science magazine, "Journal of Cell Biology."
Somatic stem cells are a type of cell in an organ that can multiply and develop into a variety of other cells of that specific organ. Such cells cannot, however, transform into cells of other organs.
Experts have expressed hope that the method can be applied to cure renal failure in humans, noting that human kidneys have similar somatic stem cells.
"It's been confirmed that somatic stem cells in kidneys are capable of not only creating new cells but also restoring damaged organs. We may be able to develop drugs aimed at (activating) somatic stem cells," said University of Tokyo Associate Prof. Keiichi Hishikawa, a member of the research team.
The research team has identified the gene of somatic stem cells in rat kidneys, and confirmed that such cells exist only in parts of rat kidneys called stroma. The team has also discovered that somatic stem cells in kidneys are capable of developing into blood vessels and renal tubules.
In the experiment, the team transplanted 10,000 kidney somatic stem cells into the ailing kidney of each laboratory rat with renal failure.
Blood tests conducted on the rats seven days later found that their kidney functions had returned to normal.
Researchers said they believe that the transplanted somatic stem cells restored the damaged kidney cells, noting that the number of somatic stem cells in the rats had decreased to about 30 percent of that in healthy rats' kidneys.
The research team also found somatic stem cells in human kidneys extracted from kidney disease sufferers after examining the organs with the consent of the patients and the University of Tokyo Hospital's ethics committee.
The researchers are poised to study how to multiply somatic stem cells extracted from human kidneys in a bid to develop a method for returning artificially multiplied cells back to the patients' kidneys. It will also study medication aimed at activating genes that cause somatic stem cells to restore damaged kidney cells.
As of the end of 2003, about 237,000 patients with chronic renal failure were regularly undergoing artificial dialysis. (Mainichi)
Mainichi Daily News
21 June 2005
A research team led by the University of Tokyo has succeeded in curing renal failure in rats by transplanting somatic stem cells of kidneys from healthy rats.
The team announced the results of their research in the June 20 issue of a U.S. science magazine, "Journal of Cell Biology."
Somatic stem cells are a type of cell in an organ that can multiply and develop into a variety of other cells of that specific organ. Such cells cannot, however, transform into cells of other organs.
Experts have expressed hope that the method can be applied to cure renal failure in humans, noting that human kidneys have similar somatic stem cells.
"It's been confirmed that somatic stem cells in kidneys are capable of not only creating new cells but also restoring damaged organs. We may be able to develop drugs aimed at (activating) somatic stem cells," said University of Tokyo Associate Prof. Keiichi Hishikawa, a member of the research team.
The research team has identified the gene of somatic stem cells in rat kidneys, and confirmed that such cells exist only in parts of rat kidneys called stroma. The team has also discovered that somatic stem cells in kidneys are capable of developing into blood vessels and renal tubules.
In the experiment, the team transplanted 10,000 kidney somatic stem cells into the ailing kidney of each laboratory rat with renal failure.
Blood tests conducted on the rats seven days later found that their kidney functions had returned to normal.
Researchers said they believe that the transplanted somatic stem cells restored the damaged kidney cells, noting that the number of somatic stem cells in the rats had decreased to about 30 percent of that in healthy rats' kidneys.
The research team also found somatic stem cells in human kidneys extracted from kidney disease sufferers after examining the organs with the consent of the patients and the University of Tokyo Hospital's ethics committee.
The researchers are poised to study how to multiply somatic stem cells extracted from human kidneys in a bid to develop a method for returning artificially multiplied cells back to the patients' kidneys. It will also study medication aimed at activating genes that cause somatic stem cells to restore damaged kidney cells.
As of the end of 2003, about 237,000 patients with chronic renal failure were regularly undergoing artificial dialysis. (Mainichi)
B.C. man paralyzed after flu shot warns of risks
B.C. man paralyzed after flu shot warns of risks
Last Updated: Wednesday, October 22, 2008 | 3:58 PM ET Comments94Recommend94
CBC News
Health officials say the benefits of the influenza vaccine outweigh the risks, especially for the very young and old, and those with health problems. (Chuck Stoody/CP)
A New Westminster man is raising a warning flag after he contracted a rare and debilitating condition linked to the flu shot that left him paralyzed for almost five months.
Every fall, health care workers across Canada distribute 10 million influenza vaccinations, and for the vast majority of people, the flu shot causes no major problems.
Within two weeks of getting his annual flu shot in 2007, however, Richard Ryan, 44, went from being happy and healthy to being in excruciating pain.
At first, Ryan thought he had injured his back, and he checked into the local hospital emergency room, he told CBC News on Wednesday.
But Ryan was also suffering some numbness, and when a neurologist tested his reflexes, he found Ryan had none, he said.
"The doctor asked me what was going on in my life. And as soon as I said I was feeling ill after getting a flu shot, he said, 'Stop right there, I know what you have,'" Ryan said.
Guillain-Barré syndrome linked to vaccine
The neurologist diagnosed Ryan with Guillain-Barré syndrome, an autoimmune disease that attacks the nervous system.
According to the B.C. Centre for Disease Control, the chance of developing that particular disease from a flu shot is one in a million.
But as Ryan learned the consequences can be severe. By the time the emergency room exam was over, he was unable to get up. He spent the next 10 weeks recovering in hospital, including three weeks in intensive care, barely able to breathe or eat for himself.
"My face was paralyzed. I had no feeling inside my mouth. I couldn't feel my tongue. My left eye wouldn't close so it had to be taped shut to sleep," he said.
The illness progressed into a lifelong condition known as chronic inflammatory demyelinating polyneuropathy (CIDP), and a year later he remains heavily medicated, unable to work, and has memory problems.
Although the disease is in remission, he is not expected to make a full recovery, and the chronic condition could return at any point in the future.
Worth the risk?
Now Ryan say he is concerned that public health officials are promoting the flu vaccine while most people are not fully aware of the risks.
However, Dr. Danuta Skowronski, an epidemiologist at the B.C. Centre for Disease Control, says the benefits of the flu vaccine still outweigh the risks for the vast majority of people.
"Nothing is completely risk-free," she told CBC News. "It is always a matter of weighing the benefits and the risks."
Medical information provided with flu shots does mention the one-in-a-million chance of getting Guillain-Barré syndrome.
But it is especially important for people with heart and lung problems, the elderly and the chronically ill, to get the influenza vaccine because it could save their lives, Skowronski said.
"Influenza itself can be life threatening, and it's those groups that we want to make sure are not put off from receiving influenza vaccine unnecessarily," said Skowronski.
There are more than 2000 flu-related deaths in Canada every year. Seniors, people with weak immune systems and some children are at highest risk.
More common possible side-effects of vaccinations can include fever, muscle pain and weakness.
For his part, Ryan maintains that he's a good example of the fact that the benefits of the vaccination don't always outweigh the risks.
"I think if people knew how serious the illness is, they would think twice about the flu shot," he said.
Last Updated: Wednesday, October 22, 2008 | 3:58 PM ET Comments94Recommend94
CBC News
Health officials say the benefits of the influenza vaccine outweigh the risks, especially for the very young and old, and those with health problems. (Chuck Stoody/CP)
A New Westminster man is raising a warning flag after he contracted a rare and debilitating condition linked to the flu shot that left him paralyzed for almost five months.
Every fall, health care workers across Canada distribute 10 million influenza vaccinations, and for the vast majority of people, the flu shot causes no major problems.
Within two weeks of getting his annual flu shot in 2007, however, Richard Ryan, 44, went from being happy and healthy to being in excruciating pain.
At first, Ryan thought he had injured his back, and he checked into the local hospital emergency room, he told CBC News on Wednesday.
But Ryan was also suffering some numbness, and when a neurologist tested his reflexes, he found Ryan had none, he said.
"The doctor asked me what was going on in my life. And as soon as I said I was feeling ill after getting a flu shot, he said, 'Stop right there, I know what you have,'" Ryan said.
Guillain-Barré syndrome linked to vaccine
The neurologist diagnosed Ryan with Guillain-Barré syndrome, an autoimmune disease that attacks the nervous system.
According to the B.C. Centre for Disease Control, the chance of developing that particular disease from a flu shot is one in a million.
But as Ryan learned the consequences can be severe. By the time the emergency room exam was over, he was unable to get up. He spent the next 10 weeks recovering in hospital, including three weeks in intensive care, barely able to breathe or eat for himself.
"My face was paralyzed. I had no feeling inside my mouth. I couldn't feel my tongue. My left eye wouldn't close so it had to be taped shut to sleep," he said.
The illness progressed into a lifelong condition known as chronic inflammatory demyelinating polyneuropathy (CIDP), and a year later he remains heavily medicated, unable to work, and has memory problems.
Although the disease is in remission, he is not expected to make a full recovery, and the chronic condition could return at any point in the future.
Worth the risk?
Now Ryan say he is concerned that public health officials are promoting the flu vaccine while most people are not fully aware of the risks.
However, Dr. Danuta Skowronski, an epidemiologist at the B.C. Centre for Disease Control, says the benefits of the flu vaccine still outweigh the risks for the vast majority of people.
"Nothing is completely risk-free," she told CBC News. "It is always a matter of weighing the benefits and the risks."
Medical information provided with flu shots does mention the one-in-a-million chance of getting Guillain-Barré syndrome.
But it is especially important for people with heart and lung problems, the elderly and the chronically ill, to get the influenza vaccine because it could save their lives, Skowronski said.
"Influenza itself can be life threatening, and it's those groups that we want to make sure are not put off from receiving influenza vaccine unnecessarily," said Skowronski.
There are more than 2000 flu-related deaths in Canada every year. Seniors, people with weak immune systems and some children are at highest risk.
More common possible side-effects of vaccinations can include fever, muscle pain and weakness.
For his part, Ryan maintains that he's a good example of the fact that the benefits of the vaccination don't always outweigh the risks.
"I think if people knew how serious the illness is, they would think twice about the flu shot," he said.
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