NASA managers were still evaluating Atlantis' heat shield Wednesday, a day before the space shuttle was planned to land in Florida where a forecast for thunderstorms appeared to be the main obstacle for its return. The shuttle's first landing opportunity at 1:55 p.m., EDT, on Thursday, had thunderstorms predicted to be within 34 miles of the landing strip at Kennedy Space Center and clouds within 8,000 feet, both violations of flight rules.
NASA managers also were evaluating two technical issues before signing off on the landing. The first issue dealt with material known as gap filler, which appeared to be sticking out of a wing. Engineers wanted to make sure it could withstand the heat and aerodynamics of re-entry.
The second was a thermal blanket, which had peeled back during the June 8 launch and was repaired during a spacewalk last week. Engineers had initially made a mistake about how hot the thermal blanket could get during re-entry and wanted to recheck the data, said mission management team chairman John Shannon.
Despite the two unresolved issues, plans still were being made for landing on Thursday.
'The engineering and safety teams believe there is no risk at all during re-entry,' Shannon said.
Atlantis commander Rick Sturckow told Mission Control in Houston that the weather looked fine to him as the shuttle flew 214 miles above the state.
'We're glad to hear the weather looks good from there,' Mission Control responded. 'We'll continue to watch it over the next 24 hours.'
Atlantis has seven opportunities to land over four days.
Mission Control said landing opportunities at Kennedy, the primary landing site, look slightly better on Friday and Saturday. A backup landing site in California would be considered on Friday. That backup site plus another in New Mexico would be activated Saturday if necessary.
Atlantis has enough power for its systems to orbit until Sunday, but managers want the shuttle to land by Saturday. The flight would only be extended to Sunday if there were technical problems that needed to be fixed.
During the crew's 13-day mission to the international space station, the astronauts installed a new truss segment, unfurled a new pair of power-generating solar arrays and activated a rotating joint that allows the new solar arrays to track the sun.
The mission was extended by two days to give them time to repair the thermal blanket on the shuttle that peeled back during lift off. Astronauts Danny Olivas stapled down the blanket with a medical stapler during a spacewalk. Sturckow said he was confident the repair job would hold up.
'Everything looks great,' he said Wednesday in an interview with reporters on the ground.
During their stay, Russian computers, which control orientation and oxygen production, crashed but they were revived several days later after cosmonauts Fyodor Yurchikhin and Oleg Kotov used a cable to bypass a circuit board. While docked to the station, astronauts conserved the shuttle's power in case they needed to spend an extra day at the outpost.
'When we left, they had the computers up and running,' said Sunita 'Suni' Williams, who was returning on Atlantis after spending more than six months at the space station. 'I think there are some fixes they are going to need to do, but the station is fine right now. It's back to its normal condition.'
Like any polite houseguests, Atlantis' astronauts did their best to clean up after themselves and followed the instructions of their hosts in Mission Control before landing.
'The dirty towels can be put in a laundry bag and stowed in the airlock,' Mission Control wrote in instructions sent to the crew.
While Sturckow got a haircut from Yurchikhin before leaving the space station, Williams said a haircut was the one of the many things she was looking forward to back on the ground. Williams, whose nest of raven trusses defied gravity at the space station, set the record for longest single spaceflight by a woman.
'I'm looking forward to going to the beach and hopefully taking a walk with my husband and my dog on the beach,' she said. 'I can't wait for a good piece of pizza.'
Wednesday, June 20, 2007
Cigarette Smoking Impairs Ligament Healing
Newswise - The list of reasons you shouldn't smoke has gotten longer. Researchers at Washington University School of Medicine in St. Louis are reporting that smoking interferes with ligament healing.
Studying mice with knee ligament injuries, the team discovered cigarette smoking impairs the recruitment of cells to the injury site and delays healing following ligament-repair surgery. They reported their findings in the Journal of Orthopaedic Research.
The researchers looked at the mouse medial collateral ligament (MCL), a ligament that supports the knee joint in both mice and people. Each year in the United States there are more than 20 million reported ligament injuries, and MCL injuries are the most common. They also are the most common injuries seen in competitive and recreational sports. It's not clear exactly how many MCL injuries occur annually because many go unreported.
"A lot of MCL injuries never make it to an emergency room because patients will have a sore knee but don't seek treatment," says Rick W. Wright, M.D., associate professor of orthopaedic surgery and a senior investigator on the MCL study.
Previous studies have demonstrated that the mouse provides a good paradigm for what happens in injured human knees.
"This is a good model for knee ligament injury, but it could be a model for ligament injuries anywhere in the body," says co-investigator Linda J. Sandell, Ph.D., professor of orthopaedic surgery. "It's likely the biology is transferable to other knee ligaments, elbow ligaments, shoulder ligaments, you name it."
To look at the effects of smoking, Sandell, Wright and their colleagues used a system developed at the School of Medicine in which mice are placed inside smoking chambers six days per week. The mice don't actually have cigarettes in their mouths, but they get enough passive fumes to "smoke" two cigarettes daily, the equivalent of a person smoking about four packs per day. Mice were placed in the smoking chambers for two months prior to MCL surgery and then again after surgery to mimic the behavior of humans who continue to smoke following an injury.
The researchers say athletes who smoke should keep these findings in mind before driving for a lay-up, sliding into second base or lacing up a pair of ice skates.
The soft tissue healing that occurs following ligament injuries occurs in stages. There is an immediate pooling of blood near the injury, the sort of hemorrhaging that will cause swelling right away. This initial response is followed by several days of inflammation, in which cells called macrophages flock to the injury site and secrete substances called cytokines and chemokines. Those, in turn, recruit more cells to assist in healing. That process of cellular proliferation and synthesis lasts for several days to several weeks. The final stage of healing involves remodeling of the tissue and can continue for months and even years.
An earlier study found an increase in cell density and in gene activity to produce type I collagen in the first week following MCL injury, so in this study the researchers paid close attention to cell density, biomechanical function and gene expression during the first week after MCL repair. In mice exposed to cigarette smoke, cell density was lower and type I collagen gene expression was reduced.
"Our studies also have shown a decreased macrophage response that may help explain why we see this delayed or decreased healing response," Wright says.
Between 20 and 25 percent of the U.S. population smokes. Wright and Sandell say that although the prevalence of smoking among athletes is slightly lower, a significant percentage of recreational and even professional athletes continue to smoke. Many others use chewing tobacco, which may cause some of the same effects. But that's not yet clear since the mice in this study were exposed to smoke rather than to nicotine only.
"There are two ways to do smoking studies in animal models," Sandell explains. "One looks only at a single component, like nicotine. The other way is to use a method like the one we employed that includes all of the toxins found in smoke. We think exposing the mice to cigarette smoke itself is most relevant because when people smoke, they don't get individual components. They get everything."
Sandell and Wright say their findings point to yet another reason smokers would do well to quit.
"Many patients don't want to hear it, but these results suggest that smoking affects anyone who needs ligament-repair surgery." Wright says. "I counsel surgery patients to at least try to decrease smoking because, if nothing else, that will improve the healing of their surgical incisions. Quitting smoking is good health management regardless, but in patients having this kind of surgery, there are extra advantages."
Wright and Sandell are conducting more studies. Currently they are comparing mice exposed to smoke before MCL surgery to those exposed both before and after surgery to see whether ending smoking might assist ligament healing.
"Because ligament injuries usually occur suddenly, it's unlikely people will stop smoking until after their injury," Sandell says. "So we want to learn whether smoking cessation near the time of surgery might help reverse the healing delays we saw in this study."
Gill CS, Sandell LJ, El-Zawawy HB, Wright RW. Effects of cigarette smoking on early medial collateral ligament healing in a mouse model. Journal of Orthopaedic Research, vol. 24, pp. 2141-2149. Dec. 2006.
This research was supported by grants from the National Institutes of Health and by the National Football League Charities.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Studying mice with knee ligament injuries, the team discovered cigarette smoking impairs the recruitment of cells to the injury site and delays healing following ligament-repair surgery. They reported their findings in the Journal of Orthopaedic Research.
The researchers looked at the mouse medial collateral ligament (MCL), a ligament that supports the knee joint in both mice and people. Each year in the United States there are more than 20 million reported ligament injuries, and MCL injuries are the most common. They also are the most common injuries seen in competitive and recreational sports. It's not clear exactly how many MCL injuries occur annually because many go unreported.
"A lot of MCL injuries never make it to an emergency room because patients will have a sore knee but don't seek treatment," says Rick W. Wright, M.D., associate professor of orthopaedic surgery and a senior investigator on the MCL study.
Previous studies have demonstrated that the mouse provides a good paradigm for what happens in injured human knees.
"This is a good model for knee ligament injury, but it could be a model for ligament injuries anywhere in the body," says co-investigator Linda J. Sandell, Ph.D., professor of orthopaedic surgery. "It's likely the biology is transferable to other knee ligaments, elbow ligaments, shoulder ligaments, you name it."
To look at the effects of smoking, Sandell, Wright and their colleagues used a system developed at the School of Medicine in which mice are placed inside smoking chambers six days per week. The mice don't actually have cigarettes in their mouths, but they get enough passive fumes to "smoke" two cigarettes daily, the equivalent of a person smoking about four packs per day. Mice were placed in the smoking chambers for two months prior to MCL surgery and then again after surgery to mimic the behavior of humans who continue to smoke following an injury.
The researchers say athletes who smoke should keep these findings in mind before driving for a lay-up, sliding into second base or lacing up a pair of ice skates.
The soft tissue healing that occurs following ligament injuries occurs in stages. There is an immediate pooling of blood near the injury, the sort of hemorrhaging that will cause swelling right away. This initial response is followed by several days of inflammation, in which cells called macrophages flock to the injury site and secrete substances called cytokines and chemokines. Those, in turn, recruit more cells to assist in healing. That process of cellular proliferation and synthesis lasts for several days to several weeks. The final stage of healing involves remodeling of the tissue and can continue for months and even years.
An earlier study found an increase in cell density and in gene activity to produce type I collagen in the first week following MCL injury, so in this study the researchers paid close attention to cell density, biomechanical function and gene expression during the first week after MCL repair. In mice exposed to cigarette smoke, cell density was lower and type I collagen gene expression was reduced.
"Our studies also have shown a decreased macrophage response that may help explain why we see this delayed or decreased healing response," Wright says.
Between 20 and 25 percent of the U.S. population smokes. Wright and Sandell say that although the prevalence of smoking among athletes is slightly lower, a significant percentage of recreational and even professional athletes continue to smoke. Many others use chewing tobacco, which may cause some of the same effects. But that's not yet clear since the mice in this study were exposed to smoke rather than to nicotine only.
"There are two ways to do smoking studies in animal models," Sandell explains. "One looks only at a single component, like nicotine. The other way is to use a method like the one we employed that includes all of the toxins found in smoke. We think exposing the mice to cigarette smoke itself is most relevant because when people smoke, they don't get individual components. They get everything."
Sandell and Wright say their findings point to yet another reason smokers would do well to quit.
"Many patients don't want to hear it, but these results suggest that smoking affects anyone who needs ligament-repair surgery." Wright says. "I counsel surgery patients to at least try to decrease smoking because, if nothing else, that will improve the healing of their surgical incisions. Quitting smoking is good health management regardless, but in patients having this kind of surgery, there are extra advantages."
Wright and Sandell are conducting more studies. Currently they are comparing mice exposed to smoke before MCL surgery to those exposed both before and after surgery to see whether ending smoking might assist ligament healing.
"Because ligament injuries usually occur suddenly, it's unlikely people will stop smoking until after their injury," Sandell says. "So we want to learn whether smoking cessation near the time of surgery might help reverse the healing delays we saw in this study."
Gill CS, Sandell LJ, El-Zawawy HB, Wright RW. Effects of cigarette smoking on early medial collateral ligament healing in a mouse model. Journal of Orthopaedic Research, vol. 24, pp. 2141-2149. Dec. 2006.
This research was supported by grants from the National Institutes of Health and by the National Football League Charities.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Estrogen Pills May Lessen Artery Buildup
Five years after a landmark study scared millions of women off hormones for menopause symptoms, new research suggests the pills may offer some heart benefits for certain younger women who start taking them in their 50s.
Women who took estrogen suffered less hardening of the arteries than those who took dummy pills, researchers reported in Thursday's New England Journal of Medicine.
It was the latest study in recent months to suggest that women who take hormones at the start of menopause seem to gain some health benefits beyond relief from hot flashes. That is in sharp contrast to women who raise their health risks when they take hormones in their 60s and 70s.
In general, experts' advice hasn't changed: Use hormones only as needed to treat hot flashes, sleeplessness and other symptoms at the start of menopause. And use the lowest possible dose for the shortest possible time - no longer than four or five years.
The new study is the latest attempt to sort out how menopause hormones affect the risk of cancer, Alzheimer's disease, stroke and heart problems, and whether those risks and benefits differ by age.
The research concludes that women who started taking estrogen pills in their 50s were 30 to 40 percent less likely to have measurable levels of blockage-causing calcium in the arteries that lead to the heart.
'It seems to be slowing the rate of plaque buildup,' said Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital. She is the study's lead author.
The research is based on the Women's Health Initiative, a huge federal study started in the 1990s that focused on the risks and benefits of menopause hormones for women.
One phase of the study was suspended in 2002 after researchers detected higher rates of heart attacks, strokes, breast cancer and other problems in women who took an estrogen-progestin combination pill. Many women were startled by the findings; millions stopped taking hormones.
'The heart attack issue was really the thing that surprised us all,' said Dr. Michelle Warren, a Columbia University expert who is a consultant for Wyeth Pharmaceuticals, which makes which makes top-selling hormone pills Prempro and Premarin.
Another phase of the big women's study was stopped in 2004 when researchers saw higher risks for strokes and blood clots in women who took estrogen alone. (Levels of heart disease and breast cancer were unaffected by the solo pill.)
Since then, some scientists have begun to slice the large study's data for more nuanced meaning. They note that most of the women in the study were in their 60s or 70s, several years post-menopausal when the research began. New analyses are focusing on women who were in their 50s when they joined the study.
The scientists are researching a 'timing hypothesis' that proposes that estrogen can help against clogged arteries and heart disease, but only when given before problems develop and before natural estrogen levels have been low for an extended period of time. Estrogen can trigger heart attacks in women who have advanced atherosclerosis, experts said.
Warren likened it to exercise: When started earlier in life and done regularly, it can protect a heart. 'But if I take a woman who's 63 years old, who's never exercised, and start her on it, I can kill her,' she said.
In the new research, Manson and her colleagues focused on more than 1,000 women in their 50s who had hysterectomies. Roughly a quarter of U.S. women in that age bracket have had a hysterectomy, Manson said.
The women were either on estrogen or dummy pills for an average of about 7 1/2 years. They then had cardiac scans in 2005 to check for buildup of calcium in the arteries. The women were 64 years old, on average, at the time of the scans. There was no baseline scan of the women when the study started.
One expert who consults for Wyeth, Dr. Howard Hodis of the University of Southern California, celebrated the results as evidence that estrogen - started at the right time - could be taken for decades.
Other experts said that is going too far.
'Wishful thinking,' said Dr. Jacques Rossouw, a federal researcher who oversees the Women's Health Initiative.
Risks for stroke and blood clots remain with continued hormone use, noted Dr. Nanette Wenger, an Emory University expert on heart disease in women. Still, the latest findings should provide some comfort to menopausal women who are considering taking estrogen, she said. 'This is quite an important study.'
The risk of serious heart problems for women in their 50s is low. An earlier study by Manson and others estimated that for women in that age group, 27 in 10,000 women would suffer a heart attack in a year, and 17 in 10,000 would have a stroke.
For women on estrogen, the estimates were 17 and 15, respectively, per 10,000.
Hardening of the arteries is considered a strong predictor of heart attacks, but heart attack reduction is the real goal. So far, for younger women, there is no conclusive medical evidence about the impact on heart attacks.
Women who want to prevent heart disease should focus instead on healthy eating, exercise and not smoking, Wenger said.
Manson agreed. 'Estrogen is known to have other risks and should be used only for the treatment of menopausal symptoms at the lowest dose for the shortest duration necessary,' she said.
____
On the Net:
New England Journal of Medicine: http://www.nejm.org
Women's Health Initiative study: http://www.nhlbi.nih.gov/whi/index.html
(This version CORRECTS that health risks are seen in older women no matter when they start taking hormones and that advice is to use lowest dose of hormones 'only as needed') )
Women who took estrogen suffered less hardening of the arteries than those who took dummy pills, researchers reported in Thursday's New England Journal of Medicine.
It was the latest study in recent months to suggest that women who take hormones at the start of menopause seem to gain some health benefits beyond relief from hot flashes. That is in sharp contrast to women who raise their health risks when they take hormones in their 60s and 70s.
In general, experts' advice hasn't changed: Use hormones only as needed to treat hot flashes, sleeplessness and other symptoms at the start of menopause. And use the lowest possible dose for the shortest possible time - no longer than four or five years.
The new study is the latest attempt to sort out how menopause hormones affect the risk of cancer, Alzheimer's disease, stroke and heart problems, and whether those risks and benefits differ by age.
The research concludes that women who started taking estrogen pills in their 50s were 30 to 40 percent less likely to have measurable levels of blockage-causing calcium in the arteries that lead to the heart.
'It seems to be slowing the rate of plaque buildup,' said Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital. She is the study's lead author.
The research is based on the Women's Health Initiative, a huge federal study started in the 1990s that focused on the risks and benefits of menopause hormones for women.
One phase of the study was suspended in 2002 after researchers detected higher rates of heart attacks, strokes, breast cancer and other problems in women who took an estrogen-progestin combination pill. Many women were startled by the findings; millions stopped taking hormones.
'The heart attack issue was really the thing that surprised us all,' said Dr. Michelle Warren, a Columbia University expert who is a consultant for Wyeth Pharmaceuticals, which makes which makes top-selling hormone pills Prempro and Premarin.
Another phase of the big women's study was stopped in 2004 when researchers saw higher risks for strokes and blood clots in women who took estrogen alone. (Levels of heart disease and breast cancer were unaffected by the solo pill.)
Since then, some scientists have begun to slice the large study's data for more nuanced meaning. They note that most of the women in the study were in their 60s or 70s, several years post-menopausal when the research began. New analyses are focusing on women who were in their 50s when they joined the study.
The scientists are researching a 'timing hypothesis' that proposes that estrogen can help against clogged arteries and heart disease, but only when given before problems develop and before natural estrogen levels have been low for an extended period of time. Estrogen can trigger heart attacks in women who have advanced atherosclerosis, experts said.
Warren likened it to exercise: When started earlier in life and done regularly, it can protect a heart. 'But if I take a woman who's 63 years old, who's never exercised, and start her on it, I can kill her,' she said.
In the new research, Manson and her colleagues focused on more than 1,000 women in their 50s who had hysterectomies. Roughly a quarter of U.S. women in that age bracket have had a hysterectomy, Manson said.
The women were either on estrogen or dummy pills for an average of about 7 1/2 years. They then had cardiac scans in 2005 to check for buildup of calcium in the arteries. The women were 64 years old, on average, at the time of the scans. There was no baseline scan of the women when the study started.
One expert who consults for Wyeth, Dr. Howard Hodis of the University of Southern California, celebrated the results as evidence that estrogen - started at the right time - could be taken for decades.
Other experts said that is going too far.
'Wishful thinking,' said Dr. Jacques Rossouw, a federal researcher who oversees the Women's Health Initiative.
Risks for stroke and blood clots remain with continued hormone use, noted Dr. Nanette Wenger, an Emory University expert on heart disease in women. Still, the latest findings should provide some comfort to menopausal women who are considering taking estrogen, she said. 'This is quite an important study.'
The risk of serious heart problems for women in their 50s is low. An earlier study by Manson and others estimated that for women in that age group, 27 in 10,000 women would suffer a heart attack in a year, and 17 in 10,000 would have a stroke.
For women on estrogen, the estimates were 17 and 15, respectively, per 10,000.
Hardening of the arteries is considered a strong predictor of heart attacks, but heart attack reduction is the real goal. So far, for younger women, there is no conclusive medical evidence about the impact on heart attacks.
Women who want to prevent heart disease should focus instead on healthy eating, exercise and not smoking, Wenger said.
Manson agreed. 'Estrogen is known to have other risks and should be used only for the treatment of menopausal symptoms at the lowest dose for the shortest duration necessary,' she said.
____
On the Net:
New England Journal of Medicine: http://www.nejm.org
Women's Health Initiative study: http://www.nhlbi.nih.gov/whi/index.html
(This version CORRECTS that health risks are seen in older women no matter when they start taking hormones and that advice is to use lowest dose of hormones 'only as needed') )
Drug Warning Prompts Treatment Changes for Those with Hepatitis B, HIV
Newswise - Cross-resistance alarms raised earlier this year by Johns Hopkins researchers about a widely used antiviral therapy for hepatitis B liver infections have prompted swift treatment revisions by the drug's maker and governmental agencies.
Findings by a team of Hopkins infectious disease specialists, to be published in the latest issue of The New England Journal of Medicine online June 21, showed that entecavir should not be used on its own in patients co-infected with HIV. Use of the drug led to cross-resistance to certain antiviral drugs used to treat the AIDS virus.
As a result of the study's initial presentation in February at the 2007 Conference on Retroviruses and Opportunistic Infections (CROI), Bristol-Myers Squibb, the drug's manufacturer, changed its product labeling to warn of the potential for HIV drug resistance, notified prescribing physicians and informed the U.S. Food and Drug Administration. The U.S. Department of Health and Human Services (HHS) also revised its treatment guidelines. HHS now recommends against using entecavir, better known by its brand name Baraclude, as the first option in treating hepatitis B in co-infected patients who are not already using drugs to suppress HIV.
"Many co-infected patients and their physicians are justifiably concerned about whether or not to use the drug," says senior study author Chloe Thio, M.D. She notes that more than 4 million people worldwide are believed to be infected with both viruses.
"Patients contending with both diseases should consult with their physician to see if entecavir is the right drug to treat their hepatitis B in the first place, because the drug still works against the liver disease, or if they should refrain from taking it because of the potential for HIV drug resistance," says Thio, an associate professor of medicine at The Johns Hopkins University School of Medicine.
Hepatitis B infection attacks the liver and can lead to cirrhosis, liver cancer or even death from liver failure.
"Co-infected patients already on entecavir should consult with their physician before stopping therapy and about having blood testing done to monitor for any signs of drug resistance that could potentially compromise subsequent anti-HIV therapy," she says.
In the published study, researchers documented three cases of co-infected patients from Baltimore and San Diego who were only on entecavir therapy, yet also had decreased amounts of HIV in their blood, an indication that the drug could possibly be having some impact on their HIV disease. Detailed blood analysis of two patients showed that entecavir was interfering with HIV replication and confirmed that one patient had developed the so-called M184V mutation in HIV. This mutation is known to prevent two key drugs used to fight the immune-system disease from working. Anti-HIV drugs compromised by the mutation include lamivudine, better known as 3TC, and emtricitabine.
Since the results were presented at CROI, researchers have substantiated their findings with several more cases from across the United States, including some patients whose blood has tested positive for the presence of the M184V.
Researchers say their next step is to better understand the mechanism by which entecavir interferes with the enzyme, called reverse transcriptase, which is involved in viral replication. Their goal is to better understand how drug resistance develops, including the M184V mutation. They also plan to look for evidence of any other HIV mutations.
A description of the original presentation is available on the Hopkins Web site at http://www.hopkinsmedicine.org/Press_releases/2007/02_28_07.html.
Entecavir, first marketed in March 2005, has been a leading treatment for chronic forms of hepatitis B, which can be fatal to almost a quarter of those infected if it is left untreated. More than 1.2 million Americans are infected with hepatitis B.
Other Hopkins investigators involved in this research, which was supported by funding from the National Institutes of Health, were Moira McMahon, B.Sc.; Benjamin Jilek, B.Sc.; Timothy Brennan, M.S.; Lin Shen, B.Sc.; Yan Zhou, Ph.D.; Megan Wind-Rotolo, Ph.D.; Sifie Xing; Shridhar Bhat, Ph.D.; Robert Hegarty, C.R.N.P.; Curtis Chong, B.Sc.; Jun Liu, Ph.D.; and Robert Siliciano, M.D., Ph.D. Siliciano is also a Howard Hughes Medical Institute investigator. Additional assistance from the Naval Medical Center in San Diego was provided by Braden Hale, M.D.
Findings by a team of Hopkins infectious disease specialists, to be published in the latest issue of The New England Journal of Medicine online June 21, showed that entecavir should not be used on its own in patients co-infected with HIV. Use of the drug led to cross-resistance to certain antiviral drugs used to treat the AIDS virus.
As a result of the study's initial presentation in February at the 2007 Conference on Retroviruses and Opportunistic Infections (CROI), Bristol-Myers Squibb, the drug's manufacturer, changed its product labeling to warn of the potential for HIV drug resistance, notified prescribing physicians and informed the U.S. Food and Drug Administration. The U.S. Department of Health and Human Services (HHS) also revised its treatment guidelines. HHS now recommends against using entecavir, better known by its brand name Baraclude, as the first option in treating hepatitis B in co-infected patients who are not already using drugs to suppress HIV.
"Many co-infected patients and their physicians are justifiably concerned about whether or not to use the drug," says senior study author Chloe Thio, M.D. She notes that more than 4 million people worldwide are believed to be infected with both viruses.
"Patients contending with both diseases should consult with their physician to see if entecavir is the right drug to treat their hepatitis B in the first place, because the drug still works against the liver disease, or if they should refrain from taking it because of the potential for HIV drug resistance," says Thio, an associate professor of medicine at The Johns Hopkins University School of Medicine.
Hepatitis B infection attacks the liver and can lead to cirrhosis, liver cancer or even death from liver failure.
"Co-infected patients already on entecavir should consult with their physician before stopping therapy and about having blood testing done to monitor for any signs of drug resistance that could potentially compromise subsequent anti-HIV therapy," she says.
In the published study, researchers documented three cases of co-infected patients from Baltimore and San Diego who were only on entecavir therapy, yet also had decreased amounts of HIV in their blood, an indication that the drug could possibly be having some impact on their HIV disease. Detailed blood analysis of two patients showed that entecavir was interfering with HIV replication and confirmed that one patient had developed the so-called M184V mutation in HIV. This mutation is known to prevent two key drugs used to fight the immune-system disease from working. Anti-HIV drugs compromised by the mutation include lamivudine, better known as 3TC, and emtricitabine.
Since the results were presented at CROI, researchers have substantiated their findings with several more cases from across the United States, including some patients whose blood has tested positive for the presence of the M184V.
Researchers say their next step is to better understand the mechanism by which entecavir interferes with the enzyme, called reverse transcriptase, which is involved in viral replication. Their goal is to better understand how drug resistance develops, including the M184V mutation. They also plan to look for evidence of any other HIV mutations.
A description of the original presentation is available on the Hopkins Web site at http://www.hopkinsmedicine.org/Press_releases/2007/02_28_07.html.
Entecavir, first marketed in March 2005, has been a leading treatment for chronic forms of hepatitis B, which can be fatal to almost a quarter of those infected if it is left untreated. More than 1.2 million Americans are infected with hepatitis B.
Other Hopkins investigators involved in this research, which was supported by funding from the National Institutes of Health, were Moira McMahon, B.Sc.; Benjamin Jilek, B.Sc.; Timothy Brennan, M.S.; Lin Shen, B.Sc.; Yan Zhou, Ph.D.; Megan Wind-Rotolo, Ph.D.; Sifie Xing; Shridhar Bhat, Ph.D.; Robert Hegarty, C.R.N.P.; Curtis Chong, B.Sc.; Jun Liu, Ph.D.; and Robert Siliciano, M.D., Ph.D. Siliciano is also a Howard Hughes Medical Institute investigator. Additional assistance from the Naval Medical Center in San Diego was provided by Braden Hale, M.D.
$1 Million Gift Establishes the Leonard and Fleur Harlan Clinical Scholar Award
Newswise - A gift of $1 million from Leonard and Fleur Harlan has established the Leonard and Fleur Harlan Clinical Scholar Award at Weill Cornell Medical College to support an outstanding junior faculty member in the field of neurological surgery. Dr. Roger Härtl, director of the spine program and assistant professor of neurological surgery, has been named the first Leonard and Fleur Harlan Clinical Scholar.Dr. Antonio M. Gotto Jr., dean of Weill Cornell, says, "The Harlans have been wonderful friends to the Medical College for a long time, and this gift is just the latest demonstration of their support. Dr. Härtl is the driving force behind efforts to develop a multidisciplinary approach to spinal disorders. He works closely with colleagues from the non-surgical specialties, and it is hoped that this work will expand the management of spinal disorders through new, less invasive and more effective therapies. We have great expectations for this research.""I am incredibly grateful for this award, which will enable me to devote more time to my research in spine surgery and brain trauma -- specifically pursuing research on outcomes analysis in the treatment of complex spinal disorders," says Dr. Härtl.The field of spinal surgery is a rapidly expanding area, but it needs a better system for outcomes analyses. Dr. Härtl is pursuing specific research on outcomes analysis in the treatment of complex spinal disorders. He has introduced new minimally invasive surgical techniques and stereotactic navigation for spinal surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, for which he currently is collecting outcomes data. "Fleur and I are very pleased to see our Clinical Scholar Award go to assist such an exciting area of research and such an outstanding clinician and researcher as Dr. Härtl. We're also pleased that Dean Gotto will have the flexibility he needs to place this award in other equally worthy areas of research in the future," says Leonard Harlan, a member of Weill Cornell's Board of Overseers. Leonard and Fleur Harlan have been generous supporters of the Medical College since 1989. Mr. Harlan joined the Board of Overseers in 1998 and recently served as Vice Chair of the successful $750 million capital campaign. He is a member of the Weill Cornell Physicians Organization Policy Board, and previously served as a member of the Weill Cornell Departmental Associates, an organization of lay people interested in supporting and following developments in medical research at the Medical College. In 1999, the Harlans gave $500,000 to support research in neuroscience; the conference room in the Whitney Laboratories Neuroscience floor was named in their honor.Clinical Scholars are outstanding researchers and/or clinicians in the field of medicine who embody a tradition of excellence to be passed on to future physicians and scientists for generations to come. Clinical Scholar Awards are granted for an initial period of three years to junior faculty members who are either assistant or associate professors. The appointments to these awards are renewable, at the dean's discretion, for up to an additional consecutive three-year period. Established during the recently completed capital campaign Advancing the Clinical Mission, the Clinical Scholars program connects donors directly with faculty and their research programs.
Leonard and Fleur HarlanLeonard Harlan is chairman of the Executive Committee of Castle Harlan, Inc. and a member of the Executive Committee of CHAMP, the Australian affiliate of Castle Harlan. Mr. Harlan is currently a director of a number of companies as well as The Bulgarian American Enterprise Fund, established by the U.S. Congress. Castle Harlan, Inc. is a global private equity firm he co-founded with John K. Castle in 1987 to structure, invest in, and manage corporate transactions and private corporate equity investments. From 1969 to 1995, he was chairman and chief executive officer of The Harlan Company, Inc., a real-estate investment banking and advisory firm. Mr. Harlan began his career at Donaldson, Lufkin & Jenrette in 1965, where he was a vice president and stockholder. Fleur Harlan is a trustee of the Manhattan Institute and a member of the Board of Directors of ELEM (Youth in Distress in Israel) and The Trust for Public Land. Formerly, Mrs. Harlan was a limited partner of RS Lauder, Gaspar and Co. Ltd, a partnership that founded companies in the media and telecommunications industries for ten years. She was also managing director of Central European Development Corporation, Ltd., which developed media companies and real estate in Central Europe. Prior to that, Ms. Harlan was a manager of Bain and Company, and worked in Israel as a strategic planner with Scitex Corporation. Dr. Roger HärtlDr. Härtl received his medical degree from the Ludwig-Maximilians University in Munich, Germany, in 1993. From 1994 to 1995, he served as a fellow in the Department of Surgery at Weill Cornell Medical College. The following year he held a Neurosurgical Critical Care Fellowship in the Department of Neurosurgery at Charité Hospital, Humboldt-University of Berlin in Germany. From 1997 to 1999, Dr. Härtl joined the neurosurgery program at Allegheny University Hospital of the Health Sciences in Philadelphia. He returned to NewYork-Presbyterian Hospital/Weill Cornell Medical Center for a neurosurgery residency that he completed in 2003. After a one-year spine fellowship at the Barrow Neurological Institute in Phoenix, Ariz., where he focused on complex spinal disorders, Dr. Härtl joined Weill Cornell as assistant professor of neurological surgery in 2004. In addition to his surgical practice, Dr. Härtl has published more than 40 articles -- most recently focused on his two current areas of interest, spine surgery and brain trauma.
Weill Cornell Medical CollegeWeill Cornell Medical College -- Cornell University's Medical School located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. The Medical College -- in its commitment to global health and education -- has a strong presence in such places as Qatar, Tanzania, Haiti, Brazil, Salzburg, and Turkey. With the historic Weill Cornell Medical College in Qatar, the Medical School is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the world's first clinical trial for gene therapy for Parkinson's disease, and, most recently, the first indication of bone marrow's critical role in tumor growth. For more information, visit http://www.med.cornell.edu.
Leonard and Fleur HarlanLeonard Harlan is chairman of the Executive Committee of Castle Harlan, Inc. and a member of the Executive Committee of CHAMP, the Australian affiliate of Castle Harlan. Mr. Harlan is currently a director of a number of companies as well as The Bulgarian American Enterprise Fund, established by the U.S. Congress. Castle Harlan, Inc. is a global private equity firm he co-founded with John K. Castle in 1987 to structure, invest in, and manage corporate transactions and private corporate equity investments. From 1969 to 1995, he was chairman and chief executive officer of The Harlan Company, Inc., a real-estate investment banking and advisory firm. Mr. Harlan began his career at Donaldson, Lufkin & Jenrette in 1965, where he was a vice president and stockholder. Fleur Harlan is a trustee of the Manhattan Institute and a member of the Board of Directors of ELEM (Youth in Distress in Israel) and The Trust for Public Land. Formerly, Mrs. Harlan was a limited partner of RS Lauder, Gaspar and Co. Ltd, a partnership that founded companies in the media and telecommunications industries for ten years. She was also managing director of Central European Development Corporation, Ltd., which developed media companies and real estate in Central Europe. Prior to that, Ms. Harlan was a manager of Bain and Company, and worked in Israel as a strategic planner with Scitex Corporation. Dr. Roger HärtlDr. Härtl received his medical degree from the Ludwig-Maximilians University in Munich, Germany, in 1993. From 1994 to 1995, he served as a fellow in the Department of Surgery at Weill Cornell Medical College. The following year he held a Neurosurgical Critical Care Fellowship in the Department of Neurosurgery at Charité Hospital, Humboldt-University of Berlin in Germany. From 1997 to 1999, Dr. Härtl joined the neurosurgery program at Allegheny University Hospital of the Health Sciences in Philadelphia. He returned to NewYork-Presbyterian Hospital/Weill Cornell Medical Center for a neurosurgery residency that he completed in 2003. After a one-year spine fellowship at the Barrow Neurological Institute in Phoenix, Ariz., where he focused on complex spinal disorders, Dr. Härtl joined Weill Cornell as assistant professor of neurological surgery in 2004. In addition to his surgical practice, Dr. Härtl has published more than 40 articles -- most recently focused on his two current areas of interest, spine surgery and brain trauma.
Weill Cornell Medical CollegeWeill Cornell Medical College -- Cornell University's Medical School located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. The Medical College -- in its commitment to global health and education -- has a strong presence in such places as Qatar, Tanzania, Haiti, Brazil, Salzburg, and Turkey. With the historic Weill Cornell Medical College in Qatar, the Medical School is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the world's first clinical trial for gene therapy for Parkinson's disease, and, most recently, the first indication of bone marrow's critical role in tumor growth. For more information, visit http://www.med.cornell.edu.
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