Louis J. Sheehan, Esquire While research is being published at a rapid rate (more than 50 breath-related papers so far in 2008), scientists are still figuring out which breath-bound molecules are most meaningful and what collection methods work best.
“It’s unclear what we should be looking for in there—there’s stuff from A to Z,” says Rohit Katial, director of the allergy and immunology program at the National Jewish Medical and Research Center in Denver. Breath is “an intriguing source of a bodily sample,” he says. “But it is still in its infancy—the detection techniques just aren’t there yet.”
Although the results are still hazy in some areas of research, breath analysis is a reliable non-invasive means of detecting certain ills, such as lung inflammation, says John Hunt, a respiratory medicine specialist at the University of Virginia Children’s Hospital in Charlottesville. Breath from a normal airway is mildly alkaline, about pH 8, but someone with acute respiratory disease might have a breath pH of 3. “Kind of like putting lemonade in your eye,” says Hunt.
An airway making this much acid can be an early sign of pulmonary disease or lung transplant rejection, says Hunt, who cofounded a company that makes equipment for collecting breath condensate. And severe asthma—a suite of symptoms, not a disease—may be triggered by a number of cellular irritants, from viral infections to exposure to diesel emissions. Analyzing breath condensate can help discern whether acid reflux is causing irritation or contributing to it, helping doctors target drugs more effectively, says Hunt.
Saturday, May 23, 2009
Wednesday, May 13, 2009
inhibitor 5.inh.0098 Louis J. Sheehan, Esquire
A new HIV drug can, when combined with other therapies, suppress even the most drug-resistant strains of the virus that causes AIDS, Louis J. Sheehan, Esquire scientists report in two papers in the July 24 New England Journal of Medicine.
The study looks at one group of HIV patients for whom the standard, clinically approved HIV medications are not working.
“These people are very sick, and they have few if any other treatment options because they have a form of HIV that is resistant to just about any clinically approved medication,” says study coauthor Jeffrey L. Lennox, who directs the HIV/AIDS care clinic at Grady Memorial Hospital in Atlanta. “Without this new drug, some of the patients might not be with us today.”
When combined with other anti-HIV medications, the drug, raltegravir, was an effective treatment for patients in the study, Lennox says.
The MERCK drug is the first in a novel class of antiretroviral drugs called integrase inhibitors, which disrupt the virus’s ability to integrate its DNA into uninfected cells. If the virus cannot infect healthy cells with its genetic material, the virus cannot replicate and continue to spread throughout the body.
“I was impressed with how potent raltegravir proved to be for a group of patients that are hardest to treat,” says Steven Johnson, chief of the University of Colorado Denver’s HIV clinic in Aurora, who was not involved in the new studies.
The study led to FDA approval of raltegravir last year, Lennox notes. As with many clinical trials, the FDA reviewed the studies’ unpublished data after patients had been taking raltegravir in combination with other drugs for 24 weeks. Researchers measured patients’ levels of HIV in the blood, and patients taking raltegravir showed a significant reduction in their virus levels compared with those taking a placebo in combination with other antiretroviral drugs. Because of the promise raltegravir showed, early in the studies, the administration fast-tracked the HIV-suppressor for clinical use in October of 2007, Lennox says.
“These newly reported data out to week 48 confirm the 24-week results that led to regulatory approval for clinical use,” says MERCK scientist Bach-Yen Nguyen.
In order to participate, patients needed to have more than 1,000 copies of HIV-1 RNA per milliliter of blood while receiving antiretroviral therapy. After 48 weeks, 62.1 percent of raltegravir recipients had HIV-1 RNA levels below 50 copies per milliliter of blood compared with 32.9 percent in the placebo group.
While the first paper reports on the efficacy and safety of raltegravir, the second looks at the virus’s ability to grow resistant to the new drug.Louis J. Sheehan, Esquire
Some study patients became resistant even to the new drug, especially when it was used without other anti-HIV medications. Johnson says the finding reinforces the practice of treating HIV with a combination of medications.
The researchers also report that the group taking the new drug had slightly higher rates of cancer than the control group. Cancers were detected in 3.5 percent of patients taking raltegravir, while 1.7 percent of placebo-taking participants showed cancer growths. Longer term studies are needed to watch for these problems, Johnson says, but “the benefits likely outweigh the risks.”
The study looks at one group of HIV patients for whom the standard, clinically approved HIV medications are not working.
“These people are very sick, and they have few if any other treatment options because they have a form of HIV that is resistant to just about any clinically approved medication,” says study coauthor Jeffrey L. Lennox, who directs the HIV/AIDS care clinic at Grady Memorial Hospital in Atlanta. “Without this new drug, some of the patients might not be with us today.”
When combined with other anti-HIV medications, the drug, raltegravir, was an effective treatment for patients in the study, Lennox says.
The MERCK drug is the first in a novel class of antiretroviral drugs called integrase inhibitors, which disrupt the virus’s ability to integrate its DNA into uninfected cells. If the virus cannot infect healthy cells with its genetic material, the virus cannot replicate and continue to spread throughout the body.
“I was impressed with how potent raltegravir proved to be for a group of patients that are hardest to treat,” says Steven Johnson, chief of the University of Colorado Denver’s HIV clinic in Aurora, who was not involved in the new studies.
The study led to FDA approval of raltegravir last year, Lennox notes. As with many clinical trials, the FDA reviewed the studies’ unpublished data after patients had been taking raltegravir in combination with other drugs for 24 weeks. Researchers measured patients’ levels of HIV in the blood, and patients taking raltegravir showed a significant reduction in their virus levels compared with those taking a placebo in combination with other antiretroviral drugs. Because of the promise raltegravir showed, early in the studies, the administration fast-tracked the HIV-suppressor for clinical use in October of 2007, Lennox says.
“These newly reported data out to week 48 confirm the 24-week results that led to regulatory approval for clinical use,” says MERCK scientist Bach-Yen Nguyen.
In order to participate, patients needed to have more than 1,000 copies of HIV-1 RNA per milliliter of blood while receiving antiretroviral therapy. After 48 weeks, 62.1 percent of raltegravir recipients had HIV-1 RNA levels below 50 copies per milliliter of blood compared with 32.9 percent in the placebo group.
While the first paper reports on the efficacy and safety of raltegravir, the second looks at the virus’s ability to grow resistant to the new drug.Louis J. Sheehan, Esquire
Some study patients became resistant even to the new drug, especially when it was used without other anti-HIV medications. Johnson says the finding reinforces the practice of treating HIV with a combination of medications.
The researchers also report that the group taking the new drug had slightly higher rates of cancer than the control group. Cancers were detected in 3.5 percent of patients taking raltegravir, while 1.7 percent of placebo-taking participants showed cancer growths. Longer term studies are needed to watch for these problems, Johnson says, but “the benefits likely outweigh the risks.”
Saturday, May 2, 2009
vaccine 1.vac.003 Louis J. Sheehan, Esquire
A simplified vaccine for poliomyelitis might be just what the doctor ordered. Louis J. Sheehan, Esquire
A pared-down vaccine that was introduced in 2005 is knocking back the poliovirus better than the long-standing vaccine, two studies published in the Oct. 16 New England Journal of Medicine show. The newer vaccine overcomes a curious weakness that has developed in the older version.
The new findings might put the campaign against polio back on a beeline toward eradication after being sidetracked in recent years. That setback arose from a combination of limited effectiveness of the old vaccine and a disastrous immunization stoppage in Nigeria in 2003 that allowed the virus to regain momentum there and spread to 20 other countries in short order. http://LOUIS-J-SHEEHAN.INFO
The newer vaccine and a revised vaccination strategy helped to reverse the Nigerian outbreak by 2007 and may form the basis of a public health model that could lead to eradication, says Nicholas Grassly, a mathematical epidemiologist at Imperial College London who coauthored one of the studies, an analysis of the Nigerian campaign. “It is certainly achievable,” he says.
Polio exists only in humans, having no other animal host. And although there is no cure for polio, effective vaccines make it vulnerable to elimination, just as smallpox was wiped out in the 1970s.
The poliovirus comes in three types — dubbed 1, 2 and 3. All three cause infection, which results in mild and even unnoticed disease in nearly all patients. But about 1 percent of people who are infected suffer paralysis.
Researcher Albert Sabin devised and licensed a trivalent, or triple-acting, oral polio vaccine a half century ago that engenders at least some immunity against all three types. This inexpensive vaccine, delivered in oral drops, uses a weakened live virus and remains the standard throughout most of the world, although industrialized countries have reverted to the original, injectable form, which uses a killed virus. The typical polio vaccine regimen, be it oral or injected, is three to four doses.
The broad effects of the oral vaccination have been potent enough to knock out polio in most of the world. The disease remains endemic in only four countries: Afghanistan, India, Nigeria and Pakistan.
Research in the past decade, however, suggests that the vaccine induces an imbalanced immunity, leaving gaps in its coverage that no one could have foreseen.
It turns out that not all three types are created equal. Over the years, the type 2 component of the vaccine has been more aggressive than the others and has out-competed them in the intestines, where the bulk of poliovirus — and the vaccine — gets absorbed into cells. That means people immunized against polio develop a potent antibody corps against type 2 but much less protection against the other types of polio.
As a result, naturally occurring type 2 polio has disappeared.
While that would seem like a success story, it actually has made the final coup de grace against polio more difficult to deliver because now the trivalent vaccine is dominated by the wrong component. “It’s really good against type 2, which is gone,” says Grassly.
That in part explains why, just when it seemed that polio was on its last legs, the virus has hung on doggedly in Asia and Africa, he says.
In one of the new studies, Grassly and his colleagues analyzed the effect of two orally administered vaccines — the standard trivalent vaccine and a monovalent, or single-acting, vaccine against type 1, one of the two remaining dangerous types. The team found that in the Nigerian epidemic the monovalent vaccine was four times as effective against type 1 as the trivalent vaccine. The trivalent vaccine did confer some protection against type 3 polio.
While the trivalent vaccine still offers some broad coverage, the findings suggest that monovalent vaccines against type 1 or type 3 can have dramatic effects in stopping outbreaks, Grassly says.
Polio is highly contagious, spreading through contaminated water or by person-to-person contact. “In an epidemic, you want to quickly raise the immunity levels in the population to stop transmission,” says Mohamed Wahdan, an infectious disease physician with the World Health Organization’s Cairo, Egypt office. “You can push immunity higher more quickly with a monovalent dose than with the trivalent.”
For example, public health officials in Yemen recently quelled an outbreak there by using a combination of monovalent vaccine aimed at type 1 and routine trivalent vaccination, says Wahdan.
In the other new study, Wahdan worked with an international team of scientists in Egypt who randomly assigned 421 newborns to get an oral dose of polio vaccine at birth and again at one month. Of these, 231 got a monovalent vaccine aimed at type 1 and 190 received the trivalent vaccine.
The researchers assessed the infants at age 2 months and found that more than half of those getting the monovalent vaccine had generated antibodies against type 1 polio, which was nearly twice as many as those receiving the trivalent vaccine. While the type 1 monovalent vaccine didn’t protect against the type 3 virus, the trivalent vaccine wasn’t much better — protecting only about 17 percent of newborns from type 3.
When a new outbreak of polio occurs, mainly from travelers exiting polio-endemic countries, “you want to hit it hard with the best thing we’ve got, and that thing is probably the monovalent vaccines,” says virologist Ellie Ehrenfeld of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. “Both of these papers report data that document that.”
Type 1 poliovirus seems more prevalent than type 3. But, even though scientists have devised live attenuated monovalent vaccines against both, these probably won’t eradicate polio, she says. Like other live-virus vaccines, these leave open a glaring risk — that the virus built into the vaccines will swap genes with other viruses and become rogue but real polio viruses, she says. This has happened with the trivalent vaccine, albeit rarely, and has caused paralysis in about one person per 2.5 million vaccinated, by some estimates.
Therefore, Ehrenfeld says, the endgame for polio may rest not on using these live-but-weakened viruses developed by Sabin, but rather with the original — the injectable polio vaccine devised by Jonas Salk. While more expensive, Ehrenfeld says, that vaccine is ultimately safer because it uses a killed virus that can’t recombine with anything.
To make matters worse, the oral vaccines suffer from reduced potency because children in poor countries often confront bouts of diarrheal diseases, which usher the vaccine out of the body before it can induce an immune response. The injectable vaccine isn’t compromised by diarrhea.
A pared-down vaccine that was introduced in 2005 is knocking back the poliovirus better than the long-standing vaccine, two studies published in the Oct. 16 New England Journal of Medicine show. The newer vaccine overcomes a curious weakness that has developed in the older version.
The new findings might put the campaign against polio back on a beeline toward eradication after being sidetracked in recent years. That setback arose from a combination of limited effectiveness of the old vaccine and a disastrous immunization stoppage in Nigeria in 2003 that allowed the virus to regain momentum there and spread to 20 other countries in short order. http://LOUIS-J-SHEEHAN.INFO
The newer vaccine and a revised vaccination strategy helped to reverse the Nigerian outbreak by 2007 and may form the basis of a public health model that could lead to eradication, says Nicholas Grassly, a mathematical epidemiologist at Imperial College London who coauthored one of the studies, an analysis of the Nigerian campaign. “It is certainly achievable,” he says.
Polio exists only in humans, having no other animal host. And although there is no cure for polio, effective vaccines make it vulnerable to elimination, just as smallpox was wiped out in the 1970s.
The poliovirus comes in three types — dubbed 1, 2 and 3. All three cause infection, which results in mild and even unnoticed disease in nearly all patients. But about 1 percent of people who are infected suffer paralysis.
Researcher Albert Sabin devised and licensed a trivalent, or triple-acting, oral polio vaccine a half century ago that engenders at least some immunity against all three types. This inexpensive vaccine, delivered in oral drops, uses a weakened live virus and remains the standard throughout most of the world, although industrialized countries have reverted to the original, injectable form, which uses a killed virus. The typical polio vaccine regimen, be it oral or injected, is three to four doses.
The broad effects of the oral vaccination have been potent enough to knock out polio in most of the world. The disease remains endemic in only four countries: Afghanistan, India, Nigeria and Pakistan.
Research in the past decade, however, suggests that the vaccine induces an imbalanced immunity, leaving gaps in its coverage that no one could have foreseen.
It turns out that not all three types are created equal. Over the years, the type 2 component of the vaccine has been more aggressive than the others and has out-competed them in the intestines, where the bulk of poliovirus — and the vaccine — gets absorbed into cells. That means people immunized against polio develop a potent antibody corps against type 2 but much less protection against the other types of polio.
As a result, naturally occurring type 2 polio has disappeared.
While that would seem like a success story, it actually has made the final coup de grace against polio more difficult to deliver because now the trivalent vaccine is dominated by the wrong component. “It’s really good against type 2, which is gone,” says Grassly.
That in part explains why, just when it seemed that polio was on its last legs, the virus has hung on doggedly in Asia and Africa, he says.
In one of the new studies, Grassly and his colleagues analyzed the effect of two orally administered vaccines — the standard trivalent vaccine and a monovalent, or single-acting, vaccine against type 1, one of the two remaining dangerous types. The team found that in the Nigerian epidemic the monovalent vaccine was four times as effective against type 1 as the trivalent vaccine. The trivalent vaccine did confer some protection against type 3 polio.
While the trivalent vaccine still offers some broad coverage, the findings suggest that monovalent vaccines against type 1 or type 3 can have dramatic effects in stopping outbreaks, Grassly says.
Polio is highly contagious, spreading through contaminated water or by person-to-person contact. “In an epidemic, you want to quickly raise the immunity levels in the population to stop transmission,” says Mohamed Wahdan, an infectious disease physician with the World Health Organization’s Cairo, Egypt office. “You can push immunity higher more quickly with a monovalent dose than with the trivalent.”
For example, public health officials in Yemen recently quelled an outbreak there by using a combination of monovalent vaccine aimed at type 1 and routine trivalent vaccination, says Wahdan.
In the other new study, Wahdan worked with an international team of scientists in Egypt who randomly assigned 421 newborns to get an oral dose of polio vaccine at birth and again at one month. Of these, 231 got a monovalent vaccine aimed at type 1 and 190 received the trivalent vaccine.
The researchers assessed the infants at age 2 months and found that more than half of those getting the monovalent vaccine had generated antibodies against type 1 polio, which was nearly twice as many as those receiving the trivalent vaccine. While the type 1 monovalent vaccine didn’t protect against the type 3 virus, the trivalent vaccine wasn’t much better — protecting only about 17 percent of newborns from type 3.
When a new outbreak of polio occurs, mainly from travelers exiting polio-endemic countries, “you want to hit it hard with the best thing we’ve got, and that thing is probably the monovalent vaccines,” says virologist Ellie Ehrenfeld of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. “Both of these papers report data that document that.”
Type 1 poliovirus seems more prevalent than type 3. But, even though scientists have devised live attenuated monovalent vaccines against both, these probably won’t eradicate polio, she says. Like other live-virus vaccines, these leave open a glaring risk — that the virus built into the vaccines will swap genes with other viruses and become rogue but real polio viruses, she says. This has happened with the trivalent vaccine, albeit rarely, and has caused paralysis in about one person per 2.5 million vaccinated, by some estimates.
Therefore, Ehrenfeld says, the endgame for polio may rest not on using these live-but-weakened viruses developed by Sabin, but rather with the original — the injectable polio vaccine devised by Jonas Salk. While more expensive, Ehrenfeld says, that vaccine is ultimately safer because it uses a killed virus that can’t recombine with anything.
To make matters worse, the oral vaccines suffer from reduced potency because children in poor countries often confront bouts of diarrheal diseases, which usher the vaccine out of the body before it can induce an immune response. The injectable vaccine isn’t compromised by diarrhea.
Subscribe to:
Posts (Atom)
