Kevin's Watch

Key Component of Bio-Artificial Kidney Moves Concept Closer to Reality: Clinical Trials May Begin Soon


Researchers at the University of Michigan are developing a bio-artificial kidney that uses living kidney cells to duplicate nearly all the functions of a healthy organ. While still in the experimental stage, the bio-artificial kidney could one day provide life-saving treatment for thousands of people with serious kidney disease.



H. David Humes
"The kidney is the first human organ for which a mechanical substitute - the kidney dialysis machine - was designed," says H. David Humes, M.D., professor of internal medicine. "We believe it also will be the first organ to have a fully functioning, implantable substitute created with the new science of tissue engineering."

Humes and his U-M research team recently completed animal testing of a key component of the bio-artificial kidney, called a Renal Tubule Assist Device. This device is designed for use outside the body to treat acute kidney failure. Each year in the United States, about 190,000 people face this life-threatening condition, in which the kidneys suddenly shut down as a result of infection or injury. Individuals with acute renal failure typically spend at least 10 days in intensive care attached to a hemofiltration unit, which removes toxic waste products from their blood. Even with advanced medical care, more than 50 percent of these patients die before their kidneys can recover.

In a study published in the May, 1999, issue of Nature - Biotechnology, Humes described how the Renal Tubule Assist Device, connected to a standard hemofiltration unit, helped improve kidney function in laboratory animals with acute renal failure.

According to Humes, kidney cells lining hollow fibers in the device reabsorb vital electrolytes, water and glucose filtered out of blood during hemofiltration, in addition to producing other important molecules. Without these substances, the patient cannot fight off infections and maintain a normal fluid balance. In Humes' study, the device reabsorbed about 50 percent of water and other important molecules, an amount similar to the reabsorption capacity of a normal kidney.

Pending FDA approval, human clinical trials for the Renal Tubule Assist Device in patients with acute kidney failure could begin as early as this fall. Within five years, Humes hopes to develop additional components of the bio-artificial kidney for patients with chronic renal failure - a gradual deterioration of kidney function that currently affects over 300,000 people in the United States, a number growing by about six percent each year.

"Our goal is to bring all the components for a bio-artificial kidney together in one implantable device that will carry out all the functions of a natural kidney," Humes says. "We hope that one day it will be available as a universal-donor organ. This could eliminate the shortage of kidneys for transplant, end long waiting times for transplant organs, and replace dialysis as a treatment for chronic renal failure."

Research on the bio-artificial kidney is being conducted at the Department of Veterans Affairs Ann Arbor Healthcare System. Funding to support the research is provided by the National Institutes of Health, the VA Research Service and Nephros.

BIOLOGICAL WARFARE: Ann Arbor scientists develop defense

Substance stops germs from spreading farther
October 3, 2001




BY WENDY WENDLAND-BOWYER
FREE PRESS STAFF WRITER




The white liquid resembling skim milk that fills bottles in the back of an Ann Arbor laboratory doesn't look like a potentially powerful tool in the war against bioterrorism.

But looks can be deceiving.

Its inventors say the substance, called NanoProtect, can be sprayed or smeared on clothing, vehicles, people or anything that has been exposed to a slew of deadly substances, including anthrax spores and smallpox virus. And, they say, NanoProtect will zap the bad stuff.

"It bombards the bacteria and virus. It blows it up," said Dr. James Baker Jr., head of the University of Michigan Medical School's department of allergy and immunology. Baker, NanoProtect's chief creator, also directs the U-M's Center for Biologic Nanotechnology.

Nanotechnology, manipulating atoms and molecules, has been touted by the government as the field that will lead the next industrial revolution. It's also the science behind NanoProtect.

Baker said the new substance could have a huge impact, and he and his research team would like it to get expedited approval from the government so it can be put into the hands of the military and the public. In the weeks since the Sept. 11 terrorist attacks, researchers all over the country working on ways to thwart bioterrorists have found an increased interest -- and urgency -- surrounding their work.

A report released last week by the U.S. General Accounting Office shows the federal government will spend at least $156.8 million this fiscal year on research into technology to fight biological agents, plus an additional $347 million on preparedness. That's up from $141.2 million last year on research and $296 million on preparedness.

So many government agencies -- from the Energy Department to the Secret Service -- are doing so many things, the overall coordination is fragmented, the GAO report notes.

The Defense Department funded the research into NanoProtect with a 5-year, $11.8-million grant.

The Ann Arbor group has completed its studies and published its test results in several peer-review journals. NanoProtect also passed extensive testing at a U.S. Army site in Utah and was mentioned as a promising new product by a Defense Department official who testified before a U.S. Senate subcommittee this summer.

Despite its obvious military uses, Baker, a retired Army lieutenant colonel, said that until Sept. 11, NanoBio Corp. -- the company he and his colleagues formed to market the product -- had planned on commercial uses first.

NanoProtect can be made in 300 formulations to combat a variety of germs, including household bacteria and those that cause sexually transmitted diseases and food-borne illnesses. Testing continues on a nasal spray that could be used, for example, before boarding an airplane.

"Until terrible Tuesday, there was no . . . urgency on the government's part to adopt this," said Ted Annis, NanoBio's chief executive officer. The year "2006 was when it would have be phased in to the troops. Now it appears the time line may be advanced."

NanoProtect is made of vegetable oil and biodegradable detergents formed at the nano level. In that super-small world, objects are measured in nanometers, or 1 billionth of a meter -- 10,000 times narrower than a human hair. For NanoProtect, the technology produces droplets with a surface tension that causes them to attack and destroy the bacteria and viruses they come in contact with, Baker said.

NanoProtect would be used after a biological agent is released. With anthrax, for example, the spores can live in the air for hours, then be stirred up every time someone or something, like a car, passes by. NanoProtect could be applied to neutralize the spores.

Bleach and similar substances also can neutralize anthrax spores, but they entail environmental concerns, Baker said. NanoProtect, he said, is safe enough to rub on the skin, inhale or even swish around the mouth.

NanoBio moved into its 6,500-square-foot building a few days before Sept. 11.

Even as the seven-member staff settles in, the main focus suddenly became getting the product registered with the Food and Drug Administration and the Environmental Protection Agency. Annis said it isn't clear how long that will take. If approval is received, the plan is to make NanoProtect available to the public as quickly as possible, Annis said.

Nasty Neckties: Doctors' Ties Carry Germs

Ties Look Professional but May Carry Infection Risks for Patients

By Jeanie Lerche Davis
WebMD Medical News Reviewed By Charlotte Grayson, MD
on Monday, May 24, 2004

May 24, 2004 -- Dry clean frequently: Nearly half of all doctors' neckties carry disease-causing bacteria, a new study shows. They could spread infection among patients.


It's a wake-up call for doctors and other medical personnel. While wearing a tie looks professional, frequent cleaning should be standard practice.


"Studies such as this remind us about what we may bring to our patients' bedside," says researcher Steven J. Nurkin, with New York Hospital Medical Center of Queens.


He presented his findings at the 104th general meeting of the American Society for Microbiology in New Orleans.


In his study, Nurkin and his colleagues sampled neckties worn by male doctors, physician assistants, and medical students in a New York hospital.


During three randomly selected days, researchers collected the ties from the male clinicians in the surgical, medical, and cardiac intensive care units as well as surgical and medical floors. All the volunteers in this study were known to have daily contact with patients. Researchers also collected ties worn by hospital security guards -- people who have little interaction with patients.


And the Results Were ...


Laboratory testing showed that 20 of 42 clinicians' neckties carried bacteria, compared with 1 out of 10 of the ties worn by security guards, reports Nurkin.


In fact, a doctor was eight times more likely to carry potential disease-causing bacteria on his tie, compared with a security guard. None of the most prevalent germs was multidrug resistant, he says.


Is wearing a necktie really in the patient's best interest? Although medical staff and other hospital professionals are encouraged to wear ties, "the transmission of infection to patients ... must be considered," he says.



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SOURCE: 104th general meeting of the American Society for Microbiology, New Orleans, May 23-27, 2004.

Matrixman wrote:Fascinating article, duchess. (As Mr. Spock might say.)

What is worrisome is the article's statement that cases of chronic renal failure in the U.S. are "growing by about six percent each year." Why is this? What's the underlying cause of the increase? Does it have anything to do with the diet (or lack of a healthy one) of Americans? Pollution that is compromising people's health in general, making them more susceptible to disease?

Questions, questions...

Asbestos deaths up, climbing
Skyrocketing rate blamed on long-ago exposure
Thursday, July 22, 2004 Posted: 11:25 PM EDT (0325 GMT)


ATLANTA (AP) -- Asbestos deaths in the United States have skyrocketed since the late 1960s and will probably keep on climbing through the next decade because of long-ago exposure to the material, once widely used for insulation and fireproofing, the government said Thursday.

The Centers for Disease Control and Prevention said 1,493 people died from asbestos in 2000, compared with 77 in 1968.

In fact, in 1998, asbestos-related deaths overtook those black lung disease, reflecting in part the decline of the coal mining industry, the federal agency said.

The CDC reached its findings by reviewing the death certificates of nearly 125,000 people who had lung conditions linked to inhaling dust or fibers from minerals such as coal or asbestos.

Asbestos use in buildings increased substantially after World War II and peaked in the late 1970s and early 1980s. Because asbestos-related illnesses are slow in developing -- it can take up to 40 years between the time someone is exposed to the material and dies from it -- asbestos deaths will probably increase through the next decade, said Michael Attfield, a CDC epidemiologist.

"What you've got are folks in their 60s and 70s who might otherwise live longer, but because of the damage to their lung tissue, it leads to an early death," said Forest Horne, a Raleigh, North Carolina, lawyer who represents asbestos patients. "We're paying the price now for the use of this mineral in almost every construction insulation product used back in the '30s, '40s, '50s, '60s, all the way to the '70s."

Government regulations in the 1970s helped curb the use of asbestos. It is still used, though under heavy regulation. It is found in more than 3,000 products, including brake linings, engine gaskets and roof coatings, and is still present as insulation in older buildings.

"The disease that's being manifested now is basically the result of high exposures over a long period of time -- 20, 30, 40 years ago -- and don't reflect what current regulations requires," said Bob Pigg, president of the Asbestos Information Association of North America. "Today's products can and are being used safely."

Exposure can cause asbestosis, in which asbestos fibers get into the lungs and scar them. The lungs get stiff and it becomes difficult for them to take in air or to transfer oxygen to the blood. This can lead to frequent lung infections and heart or respiratory failure. There is no effective treatment.

Whether someone will develop asbestosis depends on such factors as the intensity and duration of exposure and the person's age when exposed.

For years, coal workers' pneumoconiosis, or black lung, was a much more common lung disease. But cases have been on the decline, possibly because fewer people are employed in the coal mining industry today, the CDC said.

Also, asbestos was probably listed on death certificates more often in recent years as health officials became aware of its dangers.

Study: Culturally adapted HIV classes benefit teen girls
From Saundra Young
CNN
Sunday, July 11, 2004 Posted: 12:52 PM EDT (1652 GMT)
(CNN) -- Learning about HIV in a positive environment with their peers could be life-saving for sexually active African-American teenage girls who are at a high risk for the virus that causes AIDS, according to a study published in the upcoming Journal of the American Medical Association.

The study was released as the weeklong 15th International AIDS Conference got underway Sunday in Bangkok, Thailand.

"Interventions for African-American adolescent girls that are gender-tailored and culturally congruent can enhance HIV-preventive behaviors, skills and mediators and may reduce pregnancy and chlamydia infection," the study by researchers at Emory University in Atlanta, Georgia, concluded.

For 2.5 years, beginning in December 1996, the researchers tested 522 African-American girls between the ages 14 to 18 who were sexually active.

According to the study, the teens were divided into two groups and attended a series of four classes that lasted four hours each.

One group of 251 girls learned about HIV, how to properly use a condom, how to negotiate the use of a condom with a sexual partner, what constitutes a healthy relationship and pride in their gender and ethnic background.

The remaining 271 girls spent the same amount of time learning about exercise and nutrition.

The researchers followed up with the teenagers after six months and a year. The girls in the HIV class reported that they were more likely to use a condom and less likely to have had a new sex partner in the past 30 days than the girls who learned about nutrition and exercise.

The study's lead author attributes the program's success to the fact that it was developed with the help of teenage girls in the community.

"They had ownership of this program" said Ralph J. DiClemente of Emory University's Rollins School of Public Health and Center for AIDS Research.

"This intervention had a motto -- be safe for yourself, for your family and your community. We wanted to instill a sense of pride in young folks," he said.

A recent study reported that HIV infection among African-American adolescent girls was significantly higher than their Caucasian and Hispanic peers, and exceeds that of white, Hispanic and black teenage males.

Sex Better Than Money for Happiness

More Money Doesn't Mean More Sex, but More Sex Can Make You Feel Richer

By Sid Kirchheimer
WebMD Feature Reviewed By Brunilda Nazario, MD




Good news for folks whose bedrooms have more activity than their bank accounts: Research shows that sex is better for your happiness than money.


That's not to say that being financially poor but sexually active is the secret to a happy life. But despite common theory, more money doesn't get you more sex, say "happiness economics" researchers.


After analyzing data on the self-reported levels of sexual activity and happiness of 16,000 people, Dartmouth College economist David Blachflower and Andrew Oswald of the University of Warwick in England report that sex "enters so strongly (and) positively in happiness equations" that they estimate increasing intercourse from once a month to once a week is equivalent to the amount of happiness generated by getting an additional $50,000 in income for the average American.


"The evidence we see is that money brings some amounts of happiness, but not as much as what economists might have thought," says Blanchflower. "We had to look to psychologists and realize that other things really matter."


Rich Man, Poor Man: What's the Difference?


Their paper, "Money, Sex, and Happiness: An Empirical Study," recently published by the National Bureau of Economic Research, essentially puts an estimated dollar amount on the happiness level resulting from sex and its trappings.


Despite popular opinion, they find that having more money doesn't mean you get more sex; there's no difference between the frequency of sex and income level. But they do find sex seems to have a greater effect on happiness levels in highly educated -- and presumingly wealthier -- people than on those with lower educational status.


Overall, the happiest folks are those getting the most sex -- married people, who report 30% more between-the-sheets action than single folks. In fact, the economists calculate that a lasting marriage equates to happiness generated by getting an extra $100,000 each year. Divorce, meanwhile, translates to a happiness depletion of $66,000 annually.


Whether that hefty happiness income boost is the result of marital bliss or more sex is up for debate. But their "econometric" calculations confirm what psychologists have long known: People who consider themselves happy are usually richer in sexual activity.


"Many studies confirm that people who are depressed have less sex," says psychologist and sex therapist Robert Hatfield, PhD, of the University of Cincinnati and a spokesman for the Society for the Scientific Study of Sexuality. "Conversely, if you're not depressed -- 'happy,' as some might say -- you're more likely to have more frequent sex."


Does sex lead to happiness, or are happy people just more likely to lead each other to the bedroom? That's still under investigation, but there is evidence that psyche and sex feed off each other.


Published July 20, 2004.



--------------------------------------------------------------------------------

SOURCES: Blachflower, D. "Money, Sex and Happiness, An Empirical Study," May 2000. David G. Blachflower, PhD, Bruce V. Raunder professor of economics, Dartmouth College, Hanover, N.H. Robert Hatfield, PhD, assistant professor of psychology, University of Cincinnati; and certified sex therapist; spokesman, Society for the Scientific Study of Sexuality.




© 2004 WebMD Inc. All rights reserved.

Psychotic mice used to study disease
Tuesday, August 31, 2004 Posted: 9:37 AM EDT (1337 GMT)

WASHINGTON (Reuters) -- Psychotic mice that flee their littermates may offer insights into diseases such as schizophrenia, U.S. researchers reported on Monday.

The genetically engineered mice have mutations in two key genes that make them psychotic, the team at University of Texas Southwestern Medical Center and Children's Hospital Medical Center in Cincinnati found.

The mutations are the same as those found in a Canadian family with a history of schizophrenia, and involve two poorly understood genes, the researchers said.

"These mice display certain deficits that are potentially consistent with schizophrenia," said Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and leader of the study.

The genes are called NPAS1 and NPAS3. The researchers mated mice that were genetically engineered to lack copies of the gene and watched the behavior of their offspring.

Those that lacked any working copy of NPAS3 were especially erratic, the researchers report in this week's issue of the Proceedings of the National Academy of Sciences.

Normally, caged mice will climb over and sniff one another, but the mice with the genetic mutations failed to socialize. One small group of the mutant mice darted around wildly, avoiding their siblings.

Both NPAS genes are expressed, or active, in brain cells called inhibitory interneurons. They control transcription factors, which are proteins that can activate or deactivate other genes. Just which genes they may control is unclear, McKnight said.

More than 2 million Americans have schizophrenia, according to the National Institute of Mental Health. The disease, which usually shows up in early adulthood, affects a patient's ability to manage emotions, interact with others and think clearly.

Patients may suffer hallucinations, delusions and disordered thinking and have a high risk of suicide. Drugs can manage the symptoms but have unpleasant side effects.

Other researchers have found genetic links to schizophrenia as well.

McKnight's team said when they examined the brains of the psychotic mice, they found abnormally low levels of a protein called reelin. Reelin is important in the embryonic development of the brain and later in life to brain cell signaling.

Other studies of people who died with with schizophrenia have found reduced levels of reelin in their brains.



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Copyright 2004 Reuters. All rights reserved.This material may not be published, broadcast, rewritten, or redistributed.

Honey, I shrunk the genome:
genome reduction in the leprosy bacillus

Getting by with the bare minimum seems to be the modus operandi of Mycobacterium leprae the causal agent of leprosy. Its genome sequence reveals that it has undergone massive genome 'downsizing' over time, discarding more than half its genes and rendering it the most striking example of genome reduction in a microbial pathogen.

The leprosy bacillus is famed for being the first microorganism definitively shown to be associated with human disease. It evades the host's immune response by invading and propagating inside the vacuoles of macrophages called phagosomes. From there, it infects the Schwann cells of the peripheral nervous system, where it disrupts myelin production, thus leading to the characteristic features of leprosy, which include skin lesions and sensory loss.

Attempts to study M. leprae have been thwarted by fruitless efforts to grow it in the laboratory. This is due in part to its excruciatingly slow growth it divides only once every two weeks, slower than any other bacterium and its requirement for an elusive cocktail of nutrients. But the sequencing of its genome by Stewart Cole and colleagues now uncovers clues to its unique metabolism and unusual 'reductive evolution'.

M. leprae seems to have completely dispensed with or substantively reduced certain metabolic pathways, including oxidative and anaerobic respiratory chains. The enzymes for breaking down host-derived lipids, a means by which many mycobacterial pathogens derive their energy, are also drastically reduced in M. leprae. By contrast, most anabolic pathways seem to be intact, indicating that M. leprae depends on these pathways to survive in the nutrient-poor microenvironment of phagosomes.

Comparison of the genome sequence of M. leprae with that of its cousin Mycobacterium tuberculosis indicates that the former has undergone substantial downsizing, losing more than 2,000 genes since its divergence from a common mycobacterial ancestor. Presumably its genes became inactivated once their functions were no longer essential to survival, and this was followed by genome shrinkage through rearrangements and deletions.

The availability of the genome sequence will aid efforts to define virulence factors of the leprosy bacillus, of which few are presently known, and will provide inroads for developing new vaccines and diagnostic tests. Also, comparative genomic analyses with M. tuberculosis are likely to yield insight into the pathogenicity of the causal agent of tuberculosis and into potential drug targets based on the set of genes crucial to the survival of both organisms.

Story by Carina Dennis, Nature Reviews Genetics

Honey, I shrunk the genome:
genome reduction in the leprosy bacillus

Getting by with the bare minimum seems to be the modus operandi of Mycobacterium leprae the causal agent of leprosy. Its genome sequence reveals that it has undergone massive genome 'downsizing' over time, discarding more than half its genes and rendering it the most striking example of genome reduction in a microbial pathogen.

The leprosy bacillus is famed for being the first microorganism definitively shown to be associated with human disease. It evades the host's immune response by invading and propagating inside the vacuoles of macrophages called phagosomes. From there, it infects the Schwann cells of the peripheral nervous system, where it disrupts myelin production, thus leading to the characteristic features of leprosy, which include skin lesions and sensory loss.

Attempts to study M. leprae have been thwarted by fruitless efforts to grow it in the laboratory. This is due in part to its excruciatingly slow growth it divides only once every two weeks, slower than any other bacterium and its requirement for an elusive cocktail of nutrients. But the sequencing of its genome by Stewart Cole and colleagues now uncovers clues to its unique metabolism and unusual 'reductive evolution'.

M. leprae seems to have completely dispensed with or substantively reduced certain metabolic pathways, including oxidative and anaerobic respiratory chains. The enzymes for breaking down host-derived lipids, a means by which many mycobacterial pathogens derive their energy, are also drastically reduced in M. leprae. By contrast, most anabolic pathways seem to be intact, indicating that M. leprae depends on these pathways to survive in the nutrient-poor microenvironment of phagosomes.

Comparison of the genome sequence of M. leprae with that of its cousin Mycobacterium tuberculosis indicates that the former has undergone substantial downsizing, losing more than 2,000 genes since its divergence from a common mycobacterial ancestor. Presumably its genes became inactivated once their functions were no longer essential to survival, and this was followed by genome shrinkage through rearrangements and deletions.

The availability of the genome sequence will aid efforts to define virulence factors of the leprosy bacillus, of which few are presently known, and will provide inroads for developing new vaccines and diagnostic tests. Also, comparative genomic analyses with M. tuberculosis are likely to yield insight into the pathogenicity of the causal agent of tuberculosis and into potential drug targets based on the set of genes crucial to the survival of both organisms.

Story by Carina Dennis, Nature Reviews Genetics

...last week the US Food and Drug Administration approved for the first time a “total artificial heart” (TAH), designed to fully replace a patient’s diseased heart until a donor heart becomes available...

...The CardioWest, which is surgically implanted in place of the heart’s own ventricles, comprises a semi-rigid housing enclosing two polyurethane ventricles, each containing a flexible diaphragm that separates two chambers.

One chamber fills with blood from one of the heart’s atria and is then ejected when air is pumped into the other chamber via pneumatic tubes connected to a large external unit.

In trials, patients who were waiting for a heart transplant but were likely to die before they got one had more than twice the chance of being alive a year later if they were given a CardioWest.

The patients were fitted with the device for an average of 79 days and their quality of life improved. Two weeks after receiving their artificial hearts, 60% could walk 30 metres or more – though they had to remain connected to the external unit. “These are very impressive results,” says Gerson Rosenberg, an artificial organ expert at Pennsylvania State University in Hershey.

Nav wrote: The nerve damage in leprosy may well be caused by the immune system detecting the presence of bacteria in the peripheral nerves and attacking them, but as nerves do not really regenerate this would leave a persistent neurological defecit.