Over the past 3 decades, percutaneous coronary intervention (PCI, or balloon angioplasty) has significantly changed the treatment of coronary artery disease (narrowing of the arteries supplying the heart muscle).
Unlike the more invasive coronary artery bypass graft (CABG) surgery, angioplasty is a nonsurgical procedure in which a tiny catheter with a balloon is inserted into the coronary artery. The balloon is then inflated to push aside the plaque causing the narrowing. Often a stent (wire mesh tube) is left in place to help keep the treated artery open; however, restenosis, or repeat narrowing, of the artery can occur over time.
Drug-eluting stents were recently introduced to lower this risk of restenosis and have become an attractive alternative to bare-metal stents. However, they are much more expensive than bare-metal stents, and studies have shown no significant differences in rates of death or heart attack between patient groups receiving either type of stent.
Two articles that will appear in the Jan. 16, 2007, issue of CMAJ provide new insights into the use of drug-eluting stents.
The first is a research article by Grilli and colleagues in which they compare the use of drug-eluting stents for PCI in public versus private sectors of the Italian medical community. They also evaluate the effect PCI with drug-eluting stents has had on the volume of cardiac surgery, including traditional CABG surgery. They found that drug-eluting stents were used more frequently in private hospitals, with public hospitals using them more sparingly and selectively in patients with high-risk coronary artery disease. Overall cardiac surgery volumes decreased significantly in the public hospitals but remained stable in the private hospitals.
The authors note that future assessments of the impact of drug-eluting stents need to consider the influence of system-wide financial and organizational incentives for adoption of their use.
In the second article, Ligthart and colleagues systematically review all published cost-effectiveness analyses comparing drug-eluting stents and bare-metal stents for PCI. They comment on how the conclusions of these analyses have differed despite using a relatively constant measure of the efficacy of drug-eluting stents. The factors they found to be associated with these different conclusions were study quality, funding source and country of origin.
In a related commentary, Knudtson examines the ongoing debates that surround the cost-effectiveness of drug-eluting stents and the clinical indications for their use. Knudtson notes that even the clinical indications for PCI have been questioned by the findings of a recent trial that has successfully challenged the long-held belief that an open artery is always worth striving for, even late in a heart attack.
Note: This story has been adapted from a news release issued by Canadian Medical Association Journal.
Source:Canadian Medical Association Journal
via Sciencedaily
Thursday, 21 December 2006
Kidney Transplantation Linked With Increased Risk Of Various Cancers
Science Daily — Following kidney transplantation, some recipients may face a 3-fold increased risk of certain cancer types, according to a study in the December 20 issue of JAMA.
Immune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer, non-Hodgkin lymphoma, and Kaposi sarcoma. Whether other cancers occur at increased rates is uncertain, because there have been few long-term population-based studies, according to background information in the article.
Claire M. Vajdic, Ph.D., of the University of New South Wales, Sydney, Australia, and colleagues compared the incidence of cancer in 28,855 patients with end-stage kidney disease (ESKD) who received renal (kidney) replacement therapy (RRT). Data were collected for three separate time periods: the 5 years before RRT, during dialysis, and after transplantation. New cancers (1982-2003) were determined by record linkage between the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Cancer Statistics Clearing House.
The researchers found that the overall incidence of cancer, excluding nonmelanoma skin cancer and those cancers known to frequently cause end-stage kidney disease, was markedly increased (3.27 times) after transplantation. In contrast, cancer incidence was only slightly increased (1.35 times) during dialysis and before RRT (1.16 times). After transplantation, cancer occurred at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18 of these sites.
"Although the incidence of some cancers was increased during dialysis, and the incidence of a few was increased before RRT, the magnitude and breadth of the increased risk after transplantation suggests that immune suppression causes a substantial and broad-ranging increase in cancer risk," the authors write.
"After kidney transplantation, a wide variety of cancers across a number of organ systems occur with substantially increased incidence. Most, but not all, of these cancers are those with known or suspected viral causes. In contrast, cancer incidence was only slightly increased before kidney transplantation. Our findings point to an important role of the interaction between common viral infections and the immune system in the etiology [cause] of cancers at a broad range of sites," the researchers conclude.
Note: This story has been adapted from a news release issued by JAMA and Archives Journals.
Source:
JAMA and Archives Journals
Immune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer, non-Hodgkin lymphoma, and Kaposi sarcoma. Whether other cancers occur at increased rates is uncertain, because there have been few long-term population-based studies, according to background information in the article.
Claire M. Vajdic, Ph.D., of the University of New South Wales, Sydney, Australia, and colleagues compared the incidence of cancer in 28,855 patients with end-stage kidney disease (ESKD) who received renal (kidney) replacement therapy (RRT). Data were collected for three separate time periods: the 5 years before RRT, during dialysis, and after transplantation. New cancers (1982-2003) were determined by record linkage between the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Cancer Statistics Clearing House.
The researchers found that the overall incidence of cancer, excluding nonmelanoma skin cancer and those cancers known to frequently cause end-stage kidney disease, was markedly increased (3.27 times) after transplantation. In contrast, cancer incidence was only slightly increased (1.35 times) during dialysis and before RRT (1.16 times). After transplantation, cancer occurred at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18 of these sites.
"Although the incidence of some cancers was increased during dialysis, and the incidence of a few was increased before RRT, the magnitude and breadth of the increased risk after transplantation suggests that immune suppression causes a substantial and broad-ranging increase in cancer risk," the authors write.
"After kidney transplantation, a wide variety of cancers across a number of organ systems occur with substantially increased incidence. Most, but not all, of these cancers are those with known or suspected viral causes. In contrast, cancer incidence was only slightly increased before kidney transplantation. Our findings point to an important role of the interaction between common viral infections and the immune system in the etiology [cause] of cancers at a broad range of sites," the researchers conclude.
Note: This story has been adapted from a news release issued by JAMA and Archives Journals.
Source:
JAMA and Archives Journals
Allergy Drug Slows Pancreatic Tumor Growth In Preclinical Studies
An anti-allergy drug in use for more than 40 years significantly reduced tumor growth in animal models of human pancreatic cancer and also increased the effectiveness of standard chemotherapy, say researchers at The University of Texas M. D. Anderson Cancer Center.
In the Dec. 20 issue of the Journal of the National Cancer Institute, the investigators report that combining the drug, cromolyn, with chemotherapy was nearly three times better at retarding growth of pancreatic tumors in mice compared to the chemotherapy agent gemcitabine alone.
The finding may lead to a treatment advance for patients with pancreatic cancer, believed to be the most lethal of all cancers. More than 95 percent of patients diagnosed with the disease die from it, and half of those deaths occur in the first six months after diagnosis.
"Our goal is to offer longer life to these patients, and the combination of these two agents may well do that," says the study's lead author, Craig Logsdon, Ph.D., a professor in the Department of Cancer Biology.
Logsdon is working with physicians at M. D. Anderson to prepare for a clinical trial. Although cromolyn is off patent and widely available, it has been used only as a topical agent (through an inhaler, nasal spray and eye drops), so the research team is studying how to deliver the drug internally.
"Cromolyn seems to reduce survival mechanisms in pancreatic cancer cells enough that when gemcitabine is added, the chemotherapy is more effective," Logsdon says. "This is good, because chemotherapy normally has very little effect in patients."
The JNCI study demonstrates in mouse models of human pancreatic cancer that the cromolyn-gemcitabine combination reduced cancer growth by 85 percent compared to control animals, Logsdon says. "Cromolyn used alone actually had a good effect on reduction of tumors compared to control animals, which surprised us," he adds. It reduced tumor growth by 70 percent, compared to growth reduction of 50 percent when gemcitabine was used as a single agent, compared to control animals.
No one knows exactly how cromolyn works to control allergies. However, Dr. Logsdon has found that cromolyn can bind a specific protein produced by cancer cells and block that protein's ability to interact with a receptor that stimulates cancer cell growth, survival, and spreading. The relationship between how the drug controls allergies and its anti-tumor effect in pancreatic cancer remains unclear. "It may be possible that cromolyn has more than one target that influences cancer," he says.
Logsdon discovered the cancer-stimulating protein, determined how it triggers tumor growth and spread, and identified cromolyn as an inhibitor. "Through serendipity and basic science sleuthing we may now have something that helps patients," he says.
The study culminates Logsdon's five-year search for an agent to treat pancreatic cancer.
Logsdon searched for genes that produced proteins secreted only by cancer cells, which would then loop around and act on the cancer cell through a receptor on the cell surface. "That way, we could have two potential drug targets - the secreted protein and the receptor," he said.
Out of a long list of such genes, Logsdon and his research team selected one called "S100P" because it is a member of the large S100 gene family, some of which produce secreted proteins and some of which are associated with other cancers. Further work showed that S100P over-expression was very specific to pancreatic cancer; the protein was not found in normal pancreatic cells. "It is important to embryonic development, but no one knows its physiological role in adult biology," he says.
By using gene-silencing techniques, Logsdon found that when the protein is disabled, cancer growth is slowed. "S100P plays a role in tumor development because it causes cancer cells to grow faster, survive better, and be more invasive," he says.
Logsdon found that S100P interacts with a receptor known as "RAGE" which also plays a role in diabetes, arthritis and Alzheimer's disease. If RAGE is blocked in pancreatic cancer cells, addition of synthetic S100P to the tumor does not accelerate growth.
While Logsdon was defining S100P in pancreatic cancer, a Japanese research team working on allergies ran an experiment to see which proteins "stuck" to anti-allergy drugs, including cromolyn. Several members of the S100 family did. Logsdon then discovered that the drug also bound to S100P. He applied cromolyn to laboratory pancreatic cancer cells, and found that tumor growth was slowed. A larger effect was seen when the chemotherapy agent gemcitabine was combined with cromolyn.
Logsdon suspects that cromolyn may have other anti-tumor effects, a theory which he is currently testing. "For me this is pretty thrilling," he says. "In a relatively short time, we have gone all the way from discovering a molecule to preparations for a clinical trial."
The study was funded by the Lockton Endowment and the M. D. Anderson Cancer Center Pancreatic SPORE grant from the National Cancer Institute. Working with Logsdon were M. D. Anderson researchers Thiruvengadam Arumugam Ph.D. and Vijaya Ramachandran, Ph.D.
Note: This story has been adapted from a news release issued by University of Texas M. D. Anderson Cancer Center.
Source:
University of Texas M. D. Anderson Cancer Center
via Sciendaily
In the Dec. 20 issue of the Journal of the National Cancer Institute, the investigators report that combining the drug, cromolyn, with chemotherapy was nearly three times better at retarding growth of pancreatic tumors in mice compared to the chemotherapy agent gemcitabine alone.
The finding may lead to a treatment advance for patients with pancreatic cancer, believed to be the most lethal of all cancers. More than 95 percent of patients diagnosed with the disease die from it, and half of those deaths occur in the first six months after diagnosis.
"Our goal is to offer longer life to these patients, and the combination of these two agents may well do that," says the study's lead author, Craig Logsdon, Ph.D., a professor in the Department of Cancer Biology.
Logsdon is working with physicians at M. D. Anderson to prepare for a clinical trial. Although cromolyn is off patent and widely available, it has been used only as a topical agent (through an inhaler, nasal spray and eye drops), so the research team is studying how to deliver the drug internally.
"Cromolyn seems to reduce survival mechanisms in pancreatic cancer cells enough that when gemcitabine is added, the chemotherapy is more effective," Logsdon says. "This is good, because chemotherapy normally has very little effect in patients."
The JNCI study demonstrates in mouse models of human pancreatic cancer that the cromolyn-gemcitabine combination reduced cancer growth by 85 percent compared to control animals, Logsdon says. "Cromolyn used alone actually had a good effect on reduction of tumors compared to control animals, which surprised us," he adds. It reduced tumor growth by 70 percent, compared to growth reduction of 50 percent when gemcitabine was used as a single agent, compared to control animals.
No one knows exactly how cromolyn works to control allergies. However, Dr. Logsdon has found that cromolyn can bind a specific protein produced by cancer cells and block that protein's ability to interact with a receptor that stimulates cancer cell growth, survival, and spreading. The relationship between how the drug controls allergies and its anti-tumor effect in pancreatic cancer remains unclear. "It may be possible that cromolyn has more than one target that influences cancer," he says.
Logsdon discovered the cancer-stimulating protein, determined how it triggers tumor growth and spread, and identified cromolyn as an inhibitor. "Through serendipity and basic science sleuthing we may now have something that helps patients," he says.
The study culminates Logsdon's five-year search for an agent to treat pancreatic cancer.
Logsdon searched for genes that produced proteins secreted only by cancer cells, which would then loop around and act on the cancer cell through a receptor on the cell surface. "That way, we could have two potential drug targets - the secreted protein and the receptor," he said.
Out of a long list of such genes, Logsdon and his research team selected one called "S100P" because it is a member of the large S100 gene family, some of which produce secreted proteins and some of which are associated with other cancers. Further work showed that S100P over-expression was very specific to pancreatic cancer; the protein was not found in normal pancreatic cells. "It is important to embryonic development, but no one knows its physiological role in adult biology," he says.
By using gene-silencing techniques, Logsdon found that when the protein is disabled, cancer growth is slowed. "S100P plays a role in tumor development because it causes cancer cells to grow faster, survive better, and be more invasive," he says.
Logsdon found that S100P interacts with a receptor known as "RAGE" which also plays a role in diabetes, arthritis and Alzheimer's disease. If RAGE is blocked in pancreatic cancer cells, addition of synthetic S100P to the tumor does not accelerate growth.
While Logsdon was defining S100P in pancreatic cancer, a Japanese research team working on allergies ran an experiment to see which proteins "stuck" to anti-allergy drugs, including cromolyn. Several members of the S100 family did. Logsdon then discovered that the drug also bound to S100P. He applied cromolyn to laboratory pancreatic cancer cells, and found that tumor growth was slowed. A larger effect was seen when the chemotherapy agent gemcitabine was combined with cromolyn.
Logsdon suspects that cromolyn may have other anti-tumor effects, a theory which he is currently testing. "For me this is pretty thrilling," he says. "In a relatively short time, we have gone all the way from discovering a molecule to preparations for a clinical trial."
The study was funded by the Lockton Endowment and the M. D. Anderson Cancer Center Pancreatic SPORE grant from the National Cancer Institute. Working with Logsdon were M. D. Anderson researchers Thiruvengadam Arumugam Ph.D. and Vijaya Ramachandran, Ph.D.
Note: This story has been adapted from a news release issued by University of Texas M. D. Anderson Cancer Center.
Source:
University of Texas M. D. Anderson Cancer Center
via Sciendaily
High Levels Of Vitamin D In Body May Decrease Risk Of Multiple Sclerosis
The possibility that vitamin D could help protect people from developing multiple sclerosis (MS) has been posited by researchers in recent decades, but evidence to support that link has been scant. In the first large-scale, prospective study to investigate the relationship between vitamin D levels and MS, researchers at the Harvard School of Public Health (HSPH) have found an association between higher levels of vitamin D in the body and a lower risk of MS. The study appears in the December 20, 2006, issue of the Journal of the American Medical Association.
If confirmed, this finding suggests that many cases of MS could be prevented by increasing vitamin D levels. Although these levels could be increased by taking supplements, before any recommendation is made it is important to establish whether we are seeing a true causal association or whether vitamin D levels are only a marker of MS risk," said Alberto Ascherio, senior author of the study and associate professor of nutrition and epidemiology at HSPH.
MS is a chronic degenerative disease of the central nervous system. It affects some 350,000 people in the U.S. and 2 million worldwide, and occurs most commonly in young adults. Women, who are affected more than men, have a lifetime risk of about 1 in 200 in the U.S. Vitamin D is a hormone manufactured naturally in the body, and its levels can be increased with exposure to sunlight, consumption of foods rich in vitamin D, such as fatty fish, and by taking supplements.
The researchers, led by Ascherio, worked in collaboration with colleagues in the U.S. Army and Navy to determine whether vitamin D levels measured in healthy young adults predict their future risk of developing MS. The investigation relied on a study population of more than 7 million individuals, whose serum samples are stored in the Department of Defense Serum Repository. Between 1992 and 2004, 257 U.S. Army and Navy personnel with at least two serum samples stored in the repository were diagnosed with MS. A control group, consisting of participants who did not develop MS, was randomly selected from the study population. Serum samples were analyzed for levels of 25-hydroxyvitamin D, a good indicator of vitamin D availability to tissues, and individuals were divided into five groups of equal size according to their average levels. Because vitamin D levels are strongly influenced by skin color, separate analyses were conducted among whites, blacks, and Hispanics.
The results showed that, among whites, MS risk declined with increasing vitamin D levels--the risk was 62% lower among individuals in the top fifth of vitamin D concentration (corresponding approximately to levels above 100 nmol/L or 40 ng/mL) than among those in the bottom fifth (approximately below 63 nmol/L or 25 ng/mL). The association was strongest among individuals who were younger than 20 when they first entered the study. No significant association was found among blacks and Hispanics, possibly because of a smaller sample size and the lower levels of vitamin D found in those groups. The average age of onset of MS cases was 28.5 years old; there was no significant difference in the results between men and women.
"The results of this study converge with a growing body of experimental evidence supporting the importance of vitamin D in regulating the immune system and suppressing autoimmune reactions, which are thought by most experts to play a key role in the development of MS," said Ascherio. Kassandra Munger, first author and a doctoral candidate in nutrition at HSPH, added, "The amount of vitamin D that is needed to reach levels associated with MS protection is largely considered safe, and in fact higher vitamin D levels could be beneficial to prevent osteoporosis and other chronic diseases."
The researchers note that there could be other possible explanations for the protective role of vitamin D. For example, it's possible that exposure to UV light from the sun--the major determinant of serum levels of 25-hydroxyvitamin D--could protect people in other ways than increased vitamin D production.
The authors suggest further studies exploring how vitamin D may protect individuals from developing MS. "Although the results of this study are quite encouraging, reasonable certainty of a protective effect of vitamin D supplements requires direct experimental evidence in a large trial. Meanwhile, we are planning to expand our study to obtain more accurate data on the importance of age and of the vitamin D levels that need to be achieved for optimal protection," said Ascherio.
The work was supported by grants from the National Institute of Neurological Disease and Stroke and by a pilot grant from the National Multiple Sclerosis Society.
Note: This story has been adapted from a news release issued by Harvard School of Public Health.
Via: Sciencedaily
If confirmed, this finding suggests that many cases of MS could be prevented by increasing vitamin D levels. Although these levels could be increased by taking supplements, before any recommendation is made it is important to establish whether we are seeing a true causal association or whether vitamin D levels are only a marker of MS risk," said Alberto Ascherio, senior author of the study and associate professor of nutrition and epidemiology at HSPH.
MS is a chronic degenerative disease of the central nervous system. It affects some 350,000 people in the U.S. and 2 million worldwide, and occurs most commonly in young adults. Women, who are affected more than men, have a lifetime risk of about 1 in 200 in the U.S. Vitamin D is a hormone manufactured naturally in the body, and its levels can be increased with exposure to sunlight, consumption of foods rich in vitamin D, such as fatty fish, and by taking supplements.
The researchers, led by Ascherio, worked in collaboration with colleagues in the U.S. Army and Navy to determine whether vitamin D levels measured in healthy young adults predict their future risk of developing MS. The investigation relied on a study population of more than 7 million individuals, whose serum samples are stored in the Department of Defense Serum Repository. Between 1992 and 2004, 257 U.S. Army and Navy personnel with at least two serum samples stored in the repository were diagnosed with MS. A control group, consisting of participants who did not develop MS, was randomly selected from the study population. Serum samples were analyzed for levels of 25-hydroxyvitamin D, a good indicator of vitamin D availability to tissues, and individuals were divided into five groups of equal size according to their average levels. Because vitamin D levels are strongly influenced by skin color, separate analyses were conducted among whites, blacks, and Hispanics.
The results showed that, among whites, MS risk declined with increasing vitamin D levels--the risk was 62% lower among individuals in the top fifth of vitamin D concentration (corresponding approximately to levels above 100 nmol/L or 40 ng/mL) than among those in the bottom fifth (approximately below 63 nmol/L or 25 ng/mL). The association was strongest among individuals who were younger than 20 when they first entered the study. No significant association was found among blacks and Hispanics, possibly because of a smaller sample size and the lower levels of vitamin D found in those groups. The average age of onset of MS cases was 28.5 years old; there was no significant difference in the results between men and women.
"The results of this study converge with a growing body of experimental evidence supporting the importance of vitamin D in regulating the immune system and suppressing autoimmune reactions, which are thought by most experts to play a key role in the development of MS," said Ascherio. Kassandra Munger, first author and a doctoral candidate in nutrition at HSPH, added, "The amount of vitamin D that is needed to reach levels associated with MS protection is largely considered safe, and in fact higher vitamin D levels could be beneficial to prevent osteoporosis and other chronic diseases."
The researchers note that there could be other possible explanations for the protective role of vitamin D. For example, it's possible that exposure to UV light from the sun--the major determinant of serum levels of 25-hydroxyvitamin D--could protect people in other ways than increased vitamin D production.
The authors suggest further studies exploring how vitamin D may protect individuals from developing MS. "Although the results of this study are quite encouraging, reasonable certainty of a protective effect of vitamin D supplements requires direct experimental evidence in a large trial. Meanwhile, we are planning to expand our study to obtain more accurate data on the importance of age and of the vitamin D levels that need to be achieved for optimal protection," said Ascherio.
The work was supported by grants from the National Institute of Neurological Disease and Stroke and by a pilot grant from the National Multiple Sclerosis Society.
Note: This story has been adapted from a news release issued by Harvard School of Public Health.
Via: Sciencedaily
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