Pain Is Symptom of Parkinson's Disease
By Michael Smith
BARI, Italy, 09 sept 2008 -- Pain should be considered as a non-motor symptom of Parkinson's disease, researchers here said.
In a multi-center case-control study, volunteers with Parkinson's experienced pain more often than did age-matched controls, mainly because of the frequency of pain associated with dystonia, according to Giovanni Defazio, M.D., Ph.D., of the University of Bari, and colleagues.
But although the frequency of non-dystonic pain was similar between the cohorts, it was significantly associated in the Parkinson's cases with the clinical onset of disease, they said in the September issue of Archives of Neurology.
The findings "support the hypothesis that pain begins at clinical onset of Parkinson's disease or thereafter as a non-motor feature of Parkinson's disease," Dr. Defazio and colleagues concluded.
The study may also have implications for understanding "pain mechanisms in Parkinson's disease and identifying specific treatment strategies," the researchers said.
They looked at pain in 402 volunteers with Parkinson's disease selected from consecutive outpatients at participating centers from Nov. 1, 2006 through March 31, 2007, and compared such variables as frequency, type, and location with 317 healthy controls.
The cohorts were similar with respect to age, sex, and years of schooling, but significantly more Parkinson's patients had depression (16.7% versus 6%, significant at P=0.001) and medical conditions associated with painful symptoms (24.6% versus 35.3%, significant at P=0.02).
The researchers found:
More patients than controls reported experiencing pain for at least three months (69.9% versus 62.8%, significant at P=0.04).
Pain associated with visible dystonia was more frequent among patients than controls (6.7% versus 0%, significant at P<0.001).
Non-dystonic pain was reported with comparable frequency by case and control subjects (66.4% versus 62.8%).
However, when the researchers considered those without pain as a reference group and asked if the pain appeared before or after a reference age, they found a significant association between Parkinson's and non-dsytonic pain arising after the reference age.
In the case of patients, the reference age was the year of onset of symptoms. It was obtained for controls by subtracting the average disease duration of case patients included in the corresponding age stratum from the age of the control.
Specifically, the analysis showed:
There was no difference between patients and controls if the pain appeared before the reference age.
Pain appeared after the reference age twice as often in patients as in controls. The odds ratio was 2.1, with a 95% confidence interval from 1.4 to 2.9, which was significant at P<0.001.
Patients were more likely to have pain from cramping and central neuropathic pain. (The odds ratios were 2.5 and 2.9, significant at P=0.005 and P=0.04.)
There was little difference in arthalgic or peripheral neuropathic pain.
Patients were more likely to have pain in the shoulder, back, leg or foot.
The researchers did not report any external support for the study, nor any disclosures.
Primary source: Archives of NeurologySource reference:Defazio G, et al "Pain as a Nonmotor Symptom of Parkinson Disease: Evidence From a Case-Control Study" Arch Neurol 2008; 65(9): 1191-1194.
Tuesday, September 09, 2008
Low B12 Linked to Brain Atrophy
By Michael Smith
OXFORD, England, 09 sept 2008-- Low levels of vitamin B12 are associated with increased rates of brain atrophy in older people, researchers here said.
In a small observational study, healthy volunteers who had low -- but still normal -- levels of the vitamin had greater brain atrophy five years later than those with higher levels, according to Anna Vogiatzoglou, M.Sc., of the University of Oxford, and colleagues.
Although the study was too small to investigate cognitive changes, the finding suggests that B12 level is "a potentially important modifiable risk factor for cognitive decline in the elderly," the researchers said in the Sept. 9 issue of Neurology.
"Many factors that affect brain health are thought to be out of our control," Vogiatzoglou said in a statement. "But this study suggests that simply adjusting our diets to consume more vitamin B12 through eating meat, fish, fortified cereals, or milk may be something we can easily adjust to prevent brain shrinkage and to perhaps save our memory."
The vitamin is necessary for the methylation of homocysteine, which leads to the formation of S-adenosylmethionine, an important methyl donor in the brain, the researchers noted.
In infants with B12 deficiency and people with errors of vitamin B12 metabolism, the deficiency of S-adenosylmethionine is associated with brain atrophy, reversible if treated, they said.
Deficiency of the vitamin has also been associated with cognitive deficits in some studies, although others have reported null results, but studies of brain atrophy in the elderly are limited, the researchers said.
To clarify the issue, they enrolled 107 people over 60 who were healthy, living in the community, and looking after themselves. They were given a detailed physical exam, their brain volume was measured by MRI, and several B12 markers were measured.
The volunteers were divided into thirds, based on their vitamin levels at baseline, with those above 386 picomoles per liter serving as a reference group for logistic regression analysis.
The other groups either had between 308 and 386 picomoles per liter or less than 308. None of the volunteers had a B12 deficiency -- defined as a serum level lower than 150 picomoles per liter.
The researchers also measured a range of other markers, but in an adjusted model only holotranscobalamin and transcobalamin saturation -- which reflect the biologically available fraction of total vitamin B12 -- remained significant.
When the process was repeated after five years, the average decline in percentage of brain volume per year was 0.69. Those in the lowest third of baseline vitamin B12 -- less than 308 picomoles per liter -- tended to lose more volume, compared with those with higher baseline levels.
Specifically, in an adjusted model:
Those in the bottom third of B12 had a six-fold increase in the risk of greater percentage brain volume loss, compared with the reference group. The odds ratio was 6.17, with a 95% confidence interval from 1.25 to 30.47, which was significant at P=0.026.
Those in the middle third were also more likely to have greater volume loss than those in the reference group. The odds ratio was 4.39, with a 95% confidence interval from 1.01 to 19.03, which was significant at P=0.048.
Those in the lower third of baseline holotranscobalamin levels -- less than 54 picomoles per liter -- were also six times more likely to have greater volume loss than the reference group, with an odds ratio of 5.99, which was significant at P=0.029.
Those in the lowest two-thirds of baseline transcobalamin saturation were six times more likely to have greater volume loss, with odds ratios of 6.64 and 6.63, which were significant at P=0.022 and P=0.029, respectively.
"Even though the sample consisted of subjects with relatively good vitamin B12 status, the study was able to find a strong association of vitamin B12 markers with brain volume loss," the researchers concluded.
The authors pointed out several limitations of the study including the small sample size and the fact that they did not investigate whether the loss in brain volume is focal or diffuse.
The also noted that "as with all cohort studies in contrast to randomized trials, we cannot exclude that residual confounding, due to unknown factors, might account for the findings."
They concluded that larger interventional studies will help to define whether optimization of vitamin B12 status will contribute to the maintenance of cognitive performance with successful aging.
The study was supported by the Alzheimer's Research Trust, the Medical Research Council, the Charles Wolfson Charitable Trust, the Norwegian Foundation for Health and Rehabilitation through the Norwegian Health Association, Axis-Shield plc, and the Johan Throne Holst Foundation for Nutrition Research.
The researchers said they had no disclosures.
Primary source: NeurologySource reference:Vogiatzoglou A, et al "Vitamin B12 status and rate of brain volume loss in community-dwelling elderly" Neurology 2008; 71: 826-832.
By Michael Smith
OXFORD, England, 09 sept 2008-- Low levels of vitamin B12 are associated with increased rates of brain atrophy in older people, researchers here said.
In a small observational study, healthy volunteers who had low -- but still normal -- levels of the vitamin had greater brain atrophy five years later than those with higher levels, according to Anna Vogiatzoglou, M.Sc., of the University of Oxford, and colleagues.
Although the study was too small to investigate cognitive changes, the finding suggests that B12 level is "a potentially important modifiable risk factor for cognitive decline in the elderly," the researchers said in the Sept. 9 issue of Neurology.
"Many factors that affect brain health are thought to be out of our control," Vogiatzoglou said in a statement. "But this study suggests that simply adjusting our diets to consume more vitamin B12 through eating meat, fish, fortified cereals, or milk may be something we can easily adjust to prevent brain shrinkage and to perhaps save our memory."
The vitamin is necessary for the methylation of homocysteine, which leads to the formation of S-adenosylmethionine, an important methyl donor in the brain, the researchers noted.
In infants with B12 deficiency and people with errors of vitamin B12 metabolism, the deficiency of S-adenosylmethionine is associated with brain atrophy, reversible if treated, they said.
Deficiency of the vitamin has also been associated with cognitive deficits in some studies, although others have reported null results, but studies of brain atrophy in the elderly are limited, the researchers said.
To clarify the issue, they enrolled 107 people over 60 who were healthy, living in the community, and looking after themselves. They were given a detailed physical exam, their brain volume was measured by MRI, and several B12 markers were measured.
The volunteers were divided into thirds, based on their vitamin levels at baseline, with those above 386 picomoles per liter serving as a reference group for logistic regression analysis.
The other groups either had between 308 and 386 picomoles per liter or less than 308. None of the volunteers had a B12 deficiency -- defined as a serum level lower than 150 picomoles per liter.
The researchers also measured a range of other markers, but in an adjusted model only holotranscobalamin and transcobalamin saturation -- which reflect the biologically available fraction of total vitamin B12 -- remained significant.
When the process was repeated after five years, the average decline in percentage of brain volume per year was 0.69. Those in the lowest third of baseline vitamin B12 -- less than 308 picomoles per liter -- tended to lose more volume, compared with those with higher baseline levels.
Specifically, in an adjusted model:
Those in the bottom third of B12 had a six-fold increase in the risk of greater percentage brain volume loss, compared with the reference group. The odds ratio was 6.17, with a 95% confidence interval from 1.25 to 30.47, which was significant at P=0.026.
Those in the middle third were also more likely to have greater volume loss than those in the reference group. The odds ratio was 4.39, with a 95% confidence interval from 1.01 to 19.03, which was significant at P=0.048.
Those in the lower third of baseline holotranscobalamin levels -- less than 54 picomoles per liter -- were also six times more likely to have greater volume loss than the reference group, with an odds ratio of 5.99, which was significant at P=0.029.
Those in the lowest two-thirds of baseline transcobalamin saturation were six times more likely to have greater volume loss, with odds ratios of 6.64 and 6.63, which were significant at P=0.022 and P=0.029, respectively.
"Even though the sample consisted of subjects with relatively good vitamin B12 status, the study was able to find a strong association of vitamin B12 markers with brain volume loss," the researchers concluded.
The authors pointed out several limitations of the study including the small sample size and the fact that they did not investigate whether the loss in brain volume is focal or diffuse.
The also noted that "as with all cohort studies in contrast to randomized trials, we cannot exclude that residual confounding, due to unknown factors, might account for the findings."
They concluded that larger interventional studies will help to define whether optimization of vitamin B12 status will contribute to the maintenance of cognitive performance with successful aging.
The study was supported by the Alzheimer's Research Trust, the Medical Research Council, the Charles Wolfson Charitable Trust, the Norwegian Foundation for Health and Rehabilitation through the Norwegian Health Association, Axis-Shield plc, and the Johan Throne Holst Foundation for Nutrition Research.
The researchers said they had no disclosures.
Primary source: NeurologySource reference:Vogiatzoglou A, et al "Vitamin B12 status and rate of brain volume loss in community-dwelling elderly" Neurology 2008; 71: 826-832.
New studies on the Mediterranean diet confirm its effectiveness for chronic disease prevention
09 sept 2008--Scientists of the Instituto de Nutrición y Tecnología de los Alimentos (Institute of Nutrition and Food Technology) of the University of Granada (UGR, Spain) have been doing research into the positive effects of Mediterranean diet's ingredients on health.
Among these works, there is a new research line about pancreatic cancer cells. Emilio Martínez de Victoria Muñoz, director of the Institute, points out that in the study 'Influence of the ingredients of the Mediterranean diet on a cell line on pancreatic cancer cells' (UGR-Junta de Andalucía) they have manipulated the composition of the cell membrane providing olive oil, fish oil or an antioxidant typical of olive oil, analysing how such cells defend themselves from the aggressions which cause pancreatic alterations".
The objective is to expose olive oil compounds (such as oleic acid) and fruit and vegetable antioxidants to "membranes of a pancreatic cancer cell line in such a way that they become more or less resistant to harmful stimulus which cause diseases such as cancer or pancreatitis".
This way, the research work intends to correlate the composition of cell membranes with more or less resistance to suffering from different types of disease. The conclusions suggest that feeding and changes in membrane composition affect cell function and can therefore influence the prevention of certain diseases.
Preventive feeding
The researchers' hypothesis "starts from considering feeding as a preventive action of the development of chronic diseases, which are the first cause of mortality and morbidity in the world at present: chronic or not contagious diseases such as cardiovascular diseases, cancer, diabetes, hypertension or osteoporosis".
Recent studies of the World Health Organization have pointed out as development factors of chronic diseases (such as obesity, diabetes or cardiovascular diseases) the combination of bad feeding practices, the lack of exercise and unhealthy habits (such tobacco consumption or excessive alcohol).
According to Martínez de Victoria, who pointed it out in one of the courses of the Mediterranean Centres of the UGR in Guadix, "WHO's projection is terrifying, as they have suggested that, in 15 years, the amount of diabetes 2 will double in the world and the incidence of different types of cancer will probably increase".
But the key is to know that, modifying these three life habits, "we can prevent up to 80% of the cardiovascular diseases and 40% of the different types of cancer. The importance of this research lies in it".
###
Note: Download the video about the release: Web format: http://prensa.ugr.es/prensadocs/videosciencia/mnezvictoria1/mnezvictoria1.wmv TV format: http://prensa.ugr.es/prensadocs/videosciencia/mnezvictoria1/mnezvictoria1.avi
09 sept 2008--Scientists of the Instituto de Nutrición y Tecnología de los Alimentos (Institute of Nutrition and Food Technology) of the University of Granada (UGR, Spain) have been doing research into the positive effects of Mediterranean diet's ingredients on health.
Among these works, there is a new research line about pancreatic cancer cells. Emilio Martínez de Victoria Muñoz, director of the Institute, points out that in the study 'Influence of the ingredients of the Mediterranean diet on a cell line on pancreatic cancer cells' (UGR-Junta de Andalucía) they have manipulated the composition of the cell membrane providing olive oil, fish oil or an antioxidant typical of olive oil, analysing how such cells defend themselves from the aggressions which cause pancreatic alterations".
The objective is to expose olive oil compounds (such as oleic acid) and fruit and vegetable antioxidants to "membranes of a pancreatic cancer cell line in such a way that they become more or less resistant to harmful stimulus which cause diseases such as cancer or pancreatitis".
This way, the research work intends to correlate the composition of cell membranes with more or less resistance to suffering from different types of disease. The conclusions suggest that feeding and changes in membrane composition affect cell function and can therefore influence the prevention of certain diseases.
Preventive feeding
The researchers' hypothesis "starts from considering feeding as a preventive action of the development of chronic diseases, which are the first cause of mortality and morbidity in the world at present: chronic or not contagious diseases such as cardiovascular diseases, cancer, diabetes, hypertension or osteoporosis".
Recent studies of the World Health Organization have pointed out as development factors of chronic diseases (such as obesity, diabetes or cardiovascular diseases) the combination of bad feeding practices, the lack of exercise and unhealthy habits (such tobacco consumption or excessive alcohol).
According to Martínez de Victoria, who pointed it out in one of the courses of the Mediterranean Centres of the UGR in Guadix, "WHO's projection is terrifying, as they have suggested that, in 15 years, the amount of diabetes 2 will double in the world and the incidence of different types of cancer will probably increase".
But the key is to know that, modifying these three life habits, "we can prevent up to 80% of the cardiovascular diseases and 40% of the different types of cancer. The importance of this research lies in it".
###
Note: Download the video about the release: Web format: http://prensa.ugr.es/prensadocs/videosciencia/mnezvictoria1/mnezvictoria1.wmv TV format: http://prensa.ugr.es/prensadocs/videosciencia/mnezvictoria1/mnezvictoria1.avi
Common painkillers lower levels of prostate cancer biomarker
09 sept 2008--But impact on a man's risk for getting prostate cancer is unclear, physicians say
Common painkillers like aspirin and ibuprofen appear to lower a man's PSA level, the blood biomarker widely used by physicians to help gauge whether a man is at risk of prostate cancer.
But the authors of the study, which appears online Sept. 8 in the journal Cancer, caution that men shouldn't take the painkillers in an effort to prevent prostate cancer just yet.
"We showed that men who regularly took certain medications like aspirin and other non-steroidal anti-inflammatory drugs, or NSAIDS, had a lower serum PSA level," said first author Eric A. Singer, M.D., M.A., a urology resident at the University of Rochester Medical Center. "But there's not enough data to say that men who took the medications were less likely to get prostate cancer. This was a limited study, and we do not know how many of those men actually got prostate cancer."
Singer's team studied the records of 1319 men over the age of 40 who took part in the 2001-2002 National Health and Nutrition Examination Survey (NHANES), a health census conducted by the Centers for Disease Control and Prevention. The team looked at the men's use of NSAIDs such as aspirin and ibuprofen, as well as the painkiller acetaminophen, and at their PSA levels. A man's level of PSA, or prostate-specific antigen, is one of many clues that physicians watch to gauge a man's risk of getting prostate cancer.
The team found that men who used NSAIDs regularly had PSA levels about 10 percent lower compared to men who did not. The team made a similar observation with acetaminophen, but the result was not statistically significant due to the lower number of men in the study taking the medication.
While it might be easy to assume that a lowered PSA level automatically translates to a lowered risk of prostate cancer, the authors stress that it's too soon to draw that conclusion.
"While our results are consistent with other research that indicates that certain painkillers may reduce a man's risk of getting prostate cancer, the new findings are preliminary and don't prove a link," said corresponding author Edwin van Wijngaarden, Ph.D., assistant professor in the Department of Community and Preventive Medicine.
Singer said that a man's PSA level can be elevated for reasons unrelated to cancer. Sometimes, for instance, while inflammation is part of a cancer process, sometimes it is not, and so it's possible that a lowered PSA reflects reduced inflammation without affecting a man's risk of prostate cancer. Another possibility is that a PSA level lowered by NSAIDs might artificially mask a man's risk of getting prostate cancer: The medications might lower the PSA, but a man's risk might stay precisely the same.
"These findings underscore the importance for doctors to know what medications their patients are on," said Singer, who is chief Urology resident at the University of Rochester Medical Center. "For instance, there are medications commonly used to treat an enlarged prostate that can result in a decreased PSA, and most physicians know that. Doctors should also be asking about patients' use of NSAIDs such as aspirin and ibuprofen.
"The data is very interesting, but it will take more research to determine how to interpret the findings. In the meantime, this shouldn't change men's behavior or prompt them to take these medications to try to prevent prostate cancer."
###
In addition to Singer and van Wijngaarden, Ganesh S. Palapattu, M.D., assistant professor of Urology and part of the James P. Wilmot Cancer Center, also took part in the study.
09 sept 2008--But impact on a man's risk for getting prostate cancer is unclear, physicians say
Common painkillers like aspirin and ibuprofen appear to lower a man's PSA level, the blood biomarker widely used by physicians to help gauge whether a man is at risk of prostate cancer.
But the authors of the study, which appears online Sept. 8 in the journal Cancer, caution that men shouldn't take the painkillers in an effort to prevent prostate cancer just yet.
"We showed that men who regularly took certain medications like aspirin and other non-steroidal anti-inflammatory drugs, or NSAIDS, had a lower serum PSA level," said first author Eric A. Singer, M.D., M.A., a urology resident at the University of Rochester Medical Center. "But there's not enough data to say that men who took the medications were less likely to get prostate cancer. This was a limited study, and we do not know how many of those men actually got prostate cancer."
Singer's team studied the records of 1319 men over the age of 40 who took part in the 2001-2002 National Health and Nutrition Examination Survey (NHANES), a health census conducted by the Centers for Disease Control and Prevention. The team looked at the men's use of NSAIDs such as aspirin and ibuprofen, as well as the painkiller acetaminophen, and at their PSA levels. A man's level of PSA, or prostate-specific antigen, is one of many clues that physicians watch to gauge a man's risk of getting prostate cancer.
The team found that men who used NSAIDs regularly had PSA levels about 10 percent lower compared to men who did not. The team made a similar observation with acetaminophen, but the result was not statistically significant due to the lower number of men in the study taking the medication.
While it might be easy to assume that a lowered PSA level automatically translates to a lowered risk of prostate cancer, the authors stress that it's too soon to draw that conclusion.
"While our results are consistent with other research that indicates that certain painkillers may reduce a man's risk of getting prostate cancer, the new findings are preliminary and don't prove a link," said corresponding author Edwin van Wijngaarden, Ph.D., assistant professor in the Department of Community and Preventive Medicine.
Singer said that a man's PSA level can be elevated for reasons unrelated to cancer. Sometimes, for instance, while inflammation is part of a cancer process, sometimes it is not, and so it's possible that a lowered PSA reflects reduced inflammation without affecting a man's risk of prostate cancer. Another possibility is that a PSA level lowered by NSAIDs might artificially mask a man's risk of getting prostate cancer: The medications might lower the PSA, but a man's risk might stay precisely the same.
"These findings underscore the importance for doctors to know what medications their patients are on," said Singer, who is chief Urology resident at the University of Rochester Medical Center. "For instance, there are medications commonly used to treat an enlarged prostate that can result in a decreased PSA, and most physicians know that. Doctors should also be asking about patients' use of NSAIDs such as aspirin and ibuprofen.
"The data is very interesting, but it will take more research to determine how to interpret the findings. In the meantime, this shouldn't change men's behavior or prompt them to take these medications to try to prevent prostate cancer."
###
In addition to Singer and van Wijngaarden, Ganesh S. Palapattu, M.D., assistant professor of Urology and part of the James P. Wilmot Cancer Center, also took part in the study.
Monday, September 08, 2008
Study challenges routine use of MRI scans to evaluate breast cancer
Test is linked to delays in treatment, increase in mastectomy rates
WASHINGTON,08 sept 2008 -- A new study suggests women with newly-diagnosed breast cancer who receive an MRI after their diagnosis face delays in starting treatment and are more likely to receive a mastectomy. The study, presented today at the 2008 ASCO Breast Cancer Symposium, also shows that despite lack of evidence of their benefit, the routine use of MRI scans in women newly diagnosed increased significantly between 2004 and 2005, and again in 2006.
"We have yet to see any evidence that MRI improves outcomes when used routinely to evaluate breast cancer, and yet more and more women are getting these scans with almost no discernable pattern," said Richard J. Bleicher, M.D., F.A.C.S., a specialist in breast cancer surgery at Fox Chase Cancer Center. "For most women, an MRI scan prior to treatment is unnecessary. MRI can be of benefit because it's more sensitive, but with the high number of false positives and costs associated with the test, more studies are needed to determine whether MRI can improve outcomes in women with breast cancer."
Bleicher and his colleagues reviewed the records of 577 breast cancer patients seen in a multidisciplinary breast clinic where they were evaluated by a radiologist, pathologist, and a surgical, radiation, and medical oncologist. Of these patients, 130 had MRIs prior to treatment.
"Those who received an MRI had a three-week delay in the start of their treatment," said Bleicher. "In addition to the treatment delay, we're concerned that the well-documented false-positive rate with MRIs may be leading – or misleading – women into choosing mastectomies."
Bleicher said many of the women would have been candidates for a lesser procedure known as a lumpectomy. "There are a few reasons why we may be seeing higher mastectomy rates when MRIs are performed. An MRI scan is very sensitive, leading to a high number of false-positive findings. Rather than having a biopsy to see if those findings are real, women and their doctors may choose mastectomy out of an abundance of caution. Other studies have demonstrated that this often represents over-treatment because many of the mastectomies are later proven by pathology to have been unnecessary."
The study also revealed that younger women were more likely to have an MRI. "In our analysis, that trend didn't correspond with various breast cancer risk factors, such as a family history of breast or ovarian cancer, nor with the characteristics of their disease," explained Bleicher.
Another research conclusion included the failure of MRIs to help surgeons decrease positive margins during surgery, another hypothesized benefit of MRI.
"MRI is a valuable tool in some women, but without evidence that routine pre-treatment MRI improves a woman's outcome, its disadvantages suggest that it should not be a routine part of patient evaluation for treatment," said Bleicher. "Greater efforts to define MRI's limitations and use are needed."
###
This study was supported by a U.S. Public Health Service grant and by an appropriation from the Commonwealth of Pennsylvania. In addition to Bleicher, other authors include Robin M. Ciocca, D.O.; Brian L. Egleston, Ph.D.; Linda Sesa, N.P.; Kathryn Evers, M.D.; and Elin Sigurdson, M.D., Ph.D., of Fox Chase Cancer Center, and Monica Morrow, M.D., of Memorial Sloan-Kettering Cancer Center. The authors report no disclosures.
New once-a-week treatment for type 2 diabetes developed by Mount Sinai researcher
Toronto, 08 sept 2008 – In a study published by the Lancet journal today, Toronto researcher Dr. Daniel Drucker reported that a new once-weekly treatment for type 2 diabetes could replace the more common twice-daily injection.
"Over two million Canadians have diabetes," said Dr. Daniel Drucker, clinician-scientist and Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital. "There is currently no available therapy for type 2 diabetes that patients can receive once a week."
The new treatment, Exenatide once weekly is the first in a new class of long-acting medications that mimic the action of GLP-1 (glucagon-like peptide), a naturally occurring hormone that is produced in the gut after eating. The report compared outcomes for patients self-injecting Exenatide once weekly against results from the conventional 14 injections a week, as in the currently available version of the drug known as Exenatide (Byetta).
In an international multicentre 6-month clinical trial involving 300 eligible patients, 75 per cent of study subjects who received the once-weekly Exenatide got their diabetes under control as defined by reaching target glucose levels. Patients treated with Exenatide once weekly also experienced fewer side effects, had no increased risk of hypoglycemia (decrease in blood sugars) and saw reductions in body weight.
Dr. Drucker has studied the gut hormone GLP-1 for over 20 years. Multiple drugs based on GLP-1 action are under active clinical development, and the new once-weekly treatment is expected to undergo Canadian regulatory review as early as 2009.
"Biomedical research reaches patients and improves lives," said Dr. Jim Woodgett, Director of Research at the Samuel Lunenfeld Research Institute. "Dr. Drucker is a world-expert in the development of peptide hormone-based therapies for the treatment of human disease and this is an excellent example of moving discovery through to therapeutic application."
###
About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre established in 1985, is one of the world's leading centres in biomedical research. Thirty-two principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women's and infants' health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit www.mshri.on.ca
Toronto, 08 sept 2008 – In a study published by the Lancet journal today, Toronto researcher Dr. Daniel Drucker reported that a new once-weekly treatment for type 2 diabetes could replace the more common twice-daily injection.
"Over two million Canadians have diabetes," said Dr. Daniel Drucker, clinician-scientist and Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital. "There is currently no available therapy for type 2 diabetes that patients can receive once a week."
The new treatment, Exenatide once weekly is the first in a new class of long-acting medications that mimic the action of GLP-1 (glucagon-like peptide), a naturally occurring hormone that is produced in the gut after eating. The report compared outcomes for patients self-injecting Exenatide once weekly against results from the conventional 14 injections a week, as in the currently available version of the drug known as Exenatide (Byetta).
In an international multicentre 6-month clinical trial involving 300 eligible patients, 75 per cent of study subjects who received the once-weekly Exenatide got their diabetes under control as defined by reaching target glucose levels. Patients treated with Exenatide once weekly also experienced fewer side effects, had no increased risk of hypoglycemia (decrease in blood sugars) and saw reductions in body weight.
Dr. Drucker has studied the gut hormone GLP-1 for over 20 years. Multiple drugs based on GLP-1 action are under active clinical development, and the new once-weekly treatment is expected to undergo Canadian regulatory review as early as 2009.
"Biomedical research reaches patients and improves lives," said Dr. Jim Woodgett, Director of Research at the Samuel Lunenfeld Research Institute. "Dr. Drucker is a world-expert in the development of peptide hormone-based therapies for the treatment of human disease and this is an excellent example of moving discovery through to therapeutic application."
###
About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre established in 1985, is one of the world's leading centres in biomedical research. Thirty-two principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women's and infants' health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit www.mshri.on.ca
Milk may help bacteria survive against low levels of antibiotics
08 sept 2008--Milk may help prevent potentially dangerous bacteria like Staphylococcus from being killed by antibiotics used to treat animals, scientists heard today (Monday 8 September 2008) at the Society for General Microbiology's Autumn meeting being held this week at Trinity College, Dublin.
Bacteria sometimes form structures called biofilms that protect them against antibiotics and the body's natural defences. Now scientists have discovered that one of the most important micro-organisms that causes mastitis in cows and sheep, called Staphylococcus, can evade the animal's defences and veterinary medicines by forming these protective biofilms. Mastitis is an infection of the udder in cattle and sheep. It is often a painful condition for the cows and can even cause death.
"Mastitis is a difficult disease to control. It causes risks for public health if people drink infected milk and is expensive for farmers as it usually causes severe milk production losses, increased treatment costs and means the animals may have to be culled," said Dr Manuela Oliveira from the Faculty of Veterinary Medicine at the Technical University of Lisbon, Portugal. "When the staphylococci produce a biofilm, the structure protects them against host defences and antibiotic treatment, allowing the bacteria to persist in the udder."
In the past, scientists studying mastitis have conducted most of their experiments under laboratory conditions rather than mimicking the conditions found in living animals. This may mean that they have missed important contributory factors. However, Dr Oliveira and her colleagues have used realistic conditions to overcome this problem.
"We have discovered that milk may also protect bacteria against low concentrations of antibiotics – in the presence of milk, three of the five antibiotics tested, penicillin, gentamicin and sulphamethoxazole combined with trimethoprim, were less effective against Staphylococcus when compared with the same experiment performed in the absence of milk," said Dr Oliveira.
The Lisbon team is currently trying to identify the correct antibiotic concentrations needed to stop biofilms forming in the first place and also the concentrations needed to destroy a biofilm that has already formed. The scientists are also looking at the influence of the forces acting inside an udder during milking to see whether these help or hinder the bacteria in producing biofilms.
"This will allow for a better control of staphylococcal mastitis, cut disease costs and give an important improvement in the protection of consumers' health," said Dr Manuela Oliveira. "If we can get the doses right, and the animals are cured quicker, we will have less antibiotic residue in the environment and the risk of bacteria such as Staphylococcus aureus developing and spreading antibiotic resistance is lower."
08 sept 2008--Milk may help prevent potentially dangerous bacteria like Staphylococcus from being killed by antibiotics used to treat animals, scientists heard today (Monday 8 September 2008) at the Society for General Microbiology's Autumn meeting being held this week at Trinity College, Dublin.
Bacteria sometimes form structures called biofilms that protect them against antibiotics and the body's natural defences. Now scientists have discovered that one of the most important micro-organisms that causes mastitis in cows and sheep, called Staphylococcus, can evade the animal's defences and veterinary medicines by forming these protective biofilms. Mastitis is an infection of the udder in cattle and sheep. It is often a painful condition for the cows and can even cause death.
"Mastitis is a difficult disease to control. It causes risks for public health if people drink infected milk and is expensive for farmers as it usually causes severe milk production losses, increased treatment costs and means the animals may have to be culled," said Dr Manuela Oliveira from the Faculty of Veterinary Medicine at the Technical University of Lisbon, Portugal. "When the staphylococci produce a biofilm, the structure protects them against host defences and antibiotic treatment, allowing the bacteria to persist in the udder."
In the past, scientists studying mastitis have conducted most of their experiments under laboratory conditions rather than mimicking the conditions found in living animals. This may mean that they have missed important contributory factors. However, Dr Oliveira and her colleagues have used realistic conditions to overcome this problem.
"We have discovered that milk may also protect bacteria against low concentrations of antibiotics – in the presence of milk, three of the five antibiotics tested, penicillin, gentamicin and sulphamethoxazole combined with trimethoprim, were less effective against Staphylococcus when compared with the same experiment performed in the absence of milk," said Dr Oliveira.
The Lisbon team is currently trying to identify the correct antibiotic concentrations needed to stop biofilms forming in the first place and also the concentrations needed to destroy a biofilm that has already formed. The scientists are also looking at the influence of the forces acting inside an udder during milking to see whether these help or hinder the bacteria in producing biofilms.
"This will allow for a better control of staphylococcal mastitis, cut disease costs and give an important improvement in the protection of consumers' health," said Dr Manuela Oliveira. "If we can get the doses right, and the animals are cured quicker, we will have less antibiotic residue in the environment and the risk of bacteria such as Staphylococcus aureus developing and spreading antibiotic resistance is lower."
Genome analysis used to decode brain cancer: study
by Marlowe Hood
08 sept 2008--US scientists have unveiled the most complete genetic profile ever attempted of glioblastoma, a common and deadly form of the brain cancer that US Senator Edward Kennedy is battling.
The research uncovered a host of genetic alterations linked to the disease, including three previously unknown mutations found in at least three-quarters of tumour samples analysed.
It may also explain why, in some cases, standard chemotherapy treatment for brain tumours works at first but then loses its ability to beat back tumour growth.
The study, published in the British journal Nature, underscores a powerful new way to study cancer: harnessing powerful computers to analyse not just suspect genes in tissue samples, but entire genomes -- each with tens of thousands of genes -- across hundreds of samples.
"The ultimate aim is to achieve a complete atlas for the genomic changes in glioblastoma," explained Lynda Chin, a researcher at the Dana-Farber Cancer Institute in Boston and a member of the Cancer Genome Atlas Research Network (TCGA), which collectively authored the study.
"It would be essentially like having a full parts list for cars so that you know everything that could go wrong," she said in an interview.
The most aggressive and common of all brain tumours, glioblastoma strikes more than 20,000 people every year in the United States, and accounts for some 13,000 deaths.
Senator Kennedy, who spoke at the Democratic Party convention last month, was diagnosed with the disease this year.
Working with brain tumour samples donated by 206 patients from across the United States, the TCGA group sequenced 601 suspect genes and compared them to the same genes from healthy tissue.
Three new genes not previously linked to glioblastoma were found guilty by association: NF1, also implicated in an inherited disorder that causes runaway tissue growth along nerves; ERBB2, closely associated with breast cancer; and PI3, known to play a role in several cancers.
Besides checking for small mutations in genes, they looked for anomolies that can promote tumour growth: large strings of missing or duplicated genetic code, problems in the way information in the DNA is "transcribed" to produce proteins, and how certain molecules -- called methyl groups -- interact with DNA.
They also evaluated the impact of treatments, to see what kind of changes -- intended or not -- certain drugs trigger.
The most unexpected finding, said Chin, was that a commonly used chemotherapy treatment called temozolomide may provoke a "resistance mechanism" that compromises genes critical for DNA repair.
The result is new tumours with a large number of DNA mutations and a higher tolerance for chemotherapy.
"This type of comprehensive, coordinated analysis of unprecedented multi-dimensional data is made possible by advanced technologies" that simply did not exist a decade ago, said John Niederhuber, Director of the National Cancer Institute.
The TCGA study, which analysed many samples but relatively few genes, was released at the same time as another study, published in the US journal Science, that coded all the genes in 22 brain tumours.
"You can make important discoveries with either approach, but ideally you want to take the strength of both," Chin told AFP.
A new generation of technologies known as single molecule sequencing is "an order of magnitude cheaper and faster" and should make that possible within several years, she said.
"We have the tumours in the bank -- when this technology comes on line, we can go back and sequence not just 600 genes but all of them, and not in 20 samples but 200 or, better yet, 500 or 1000."
The examples highlighted in what she called an interim study are "just the tip of the iceberg," she added.
The TCGA consortium has already initiated the same sort of comprehensive approach to ovarian and lung cancer.
by Marlowe Hood
08 sept 2008--US scientists have unveiled the most complete genetic profile ever attempted of glioblastoma, a common and deadly form of the brain cancer that US Senator Edward Kennedy is battling.
The research uncovered a host of genetic alterations linked to the disease, including three previously unknown mutations found in at least three-quarters of tumour samples analysed.
It may also explain why, in some cases, standard chemotherapy treatment for brain tumours works at first but then loses its ability to beat back tumour growth.
The study, published in the British journal Nature, underscores a powerful new way to study cancer: harnessing powerful computers to analyse not just suspect genes in tissue samples, but entire genomes -- each with tens of thousands of genes -- across hundreds of samples.
"The ultimate aim is to achieve a complete atlas for the genomic changes in glioblastoma," explained Lynda Chin, a researcher at the Dana-Farber Cancer Institute in Boston and a member of the Cancer Genome Atlas Research Network (TCGA), which collectively authored the study.
"It would be essentially like having a full parts list for cars so that you know everything that could go wrong," she said in an interview.
The most aggressive and common of all brain tumours, glioblastoma strikes more than 20,000 people every year in the United States, and accounts for some 13,000 deaths.
Senator Kennedy, who spoke at the Democratic Party convention last month, was diagnosed with the disease this year.
Working with brain tumour samples donated by 206 patients from across the United States, the TCGA group sequenced 601 suspect genes and compared them to the same genes from healthy tissue.
Three new genes not previously linked to glioblastoma were found guilty by association: NF1, also implicated in an inherited disorder that causes runaway tissue growth along nerves; ERBB2, closely associated with breast cancer; and PI3, known to play a role in several cancers.
Besides checking for small mutations in genes, they looked for anomolies that can promote tumour growth: large strings of missing or duplicated genetic code, problems in the way information in the DNA is "transcribed" to produce proteins, and how certain molecules -- called methyl groups -- interact with DNA.
They also evaluated the impact of treatments, to see what kind of changes -- intended or not -- certain drugs trigger.
The most unexpected finding, said Chin, was that a commonly used chemotherapy treatment called temozolomide may provoke a "resistance mechanism" that compromises genes critical for DNA repair.
The result is new tumours with a large number of DNA mutations and a higher tolerance for chemotherapy.
"This type of comprehensive, coordinated analysis of unprecedented multi-dimensional data is made possible by advanced technologies" that simply did not exist a decade ago, said John Niederhuber, Director of the National Cancer Institute.
The TCGA study, which analysed many samples but relatively few genes, was released at the same time as another study, published in the US journal Science, that coded all the genes in 22 brain tumours.
"You can make important discoveries with either approach, but ideally you want to take the strength of both," Chin told AFP.
A new generation of technologies known as single molecule sequencing is "an order of magnitude cheaper and faster" and should make that possible within several years, she said.
"We have the tumours in the bank -- when this technology comes on line, we can go back and sequence not just 600 genes but all of them, and not in 20 samples but 200 or, better yet, 500 or 1000."
The examples highlighted in what she called an interim study are "just the tip of the iceberg," she added.
The TCGA consortium has already initiated the same sort of comprehensive approach to ovarian and lung cancer.
Liver disease plagues obese adolescents
By LINDA A. JOHNSON
08 sept 2008--In a new and disturbing twist on the obesity epidemic, some overweight teenagers have severe liver damage caused by too much body fat, and a handful have needed liver transplants.
Many more may need a new liver by their 30s or 40s, say experts warning that pediatricians need to be more vigilant. The condition, which can lead to cirrhosis and liver failure or liver cancer, is being seen in kids in the United States, Europe, Australia and even some developing countries, according to a surge of recent medical studies and doctors interviewed by The Associated Press.
The American Liver Foundation and other experts estimate 2 percent to 5 percent of American children over age 5, nearly all of them obese or overweight, have the condition, called nonalcoholic fatty liver disease.
"It's clearly the most common cause of liver disease," said Dr. Ronald Sokol, head of public policy at the liver foundation and a liver specialist at Children's Hospital and University of Colorado Denver.
Some experts think as many as 10 percent of all children and half of those who are obese may suffer from it, but note that few are given the simple blood test that can signal its presence. A biopsy is the only sure way to diagnose this disease.
As fat builds up, the liver can become inflamed and then scarred over time, leading to cirrhosis, a serious condition, which in years past was mostly caused by hepatitis or drinking too much alcohol. Liver failure or liver cancer can follow, but if cirrhosis has not yet developed, fatty liver disease can be reversed through weight loss.
The disease is most common in overweight children with belly fat and certain warning signs, such as diabetes or cholesterol or heart problems. However, it's been seen in a few children of normal weight.
Genetics, diet and exercise level all play a role. It is most prevalent among Hispanics, relatively rare among African-Americans, and more common among boys than girls.
"There are people in their 30s or early 40s that will require a liver transplant" from developing the condition as a kid, predicts Dr. Jose Derdoy, head of liver transplants at Cardinal Glennon Children's Medical Center in St. Louis. He's treated a 15-year-old, 530-pound boy and many others with the condition.
Experts blame obesity, with about two-thirds of all Americans overweight. With fatty liver disease becoming more common in adults, many experts predict it will become the top cause of liver transplants by 2020.
"There aren't enough livers to go around," says Dr. Philip Rosenthal of the University of California-San Francisco Children's Hospital.
His patient, Irving Shaffino, a 15-year-old Mexican-American who lives outside Lubbock, Texas, was lucky to get a transplant a year ago. He was in end-stage cirrhosis and, at 5-feet-4 1/2, weighed 180 pounds.
Irving had been fat since age 6, thanks to a high-starch, high-fat diet of Mexican food, pizza and burgers, said his mother, Guadelupe Shaffino. At age 8, she said, he had a distended stomach and by his early teens, breathing problems kept him tethered to an oxygen tank at home.
Without health insurance, the family couldn't find a local hospital that would do a transplant.
"My son begged me, 'Don't let me die, Mommy,' so I did everything in my power to find a place to help him. Thanks be to God, we found a way," said Guadelupe Shaffino, a restaurant cook.
UCSF Children's Hospital, with money from a state health program, agreed to do the transplant. Rosenthal, who oversees the hospital's pediatric liver transplant program, took over care of Irving. The doctor said without a new liver Irving would have died, maybe within months.
"He was in bad shape," said Rosenthal.
Soon after tests were completed and Irving got on a transplant waiting list, an organ was found.
"It felt like a miracle, because people say you could be on the transplant list for years," Irving said.
Within a couple of months of the July 26, 2007 operation, Irving had weaned himself from the oxygen tank and could go on walks, although he got winded quickly.
Back home in Texas, his medications are down from 11 to four and Irving said he's replaced soda and fast food with fruit, vegetables and whole grains.
"I want to get into sports again," he said. "I want to get down to maybe 150" pounds.
Sadly, however, Irving has made little progress in losing weight. While he's grown an inch and a half since his operation, he's still obese and his weight was up to 219 last month.
Specialists say many kids diagnosed with fatty liver disease come to subsequent checkups heavier, and at best, just one in four loses significant weight, the only treatment known to stop and even reverse the disease.
"My patients that are successful, the whole family has bought in," increasing exercise and changing diet, said Dr. Stephanie Abrams, a liver and obesity specialist at Texas Children's Hospital. "The problem is that we aren't changing society in favor of becoming lean."
The scope of the disease has only been realized in recent years. Just a handful of cases were reported in medical journals in the 1980s, and in the past, many adult patients were thought to be lying when they denied drinking alcohol.
Only three liver transplants on American children with nonalcoholic fatty liver disease were recorded from 1990 through 2002; two were done last year.
"It really has been only in the last two or three years that this has become more commonplace," said Dr. Ann Scheimann, a pediatric gastroenterologist at Johns Hopkins Children's Center. "It is scary."
Like heart disease, liver disease is silent. Kids may feel fine for years. Any early symptoms, like fatigue and loss of appetite, are vague and usually eclipsed by more conspicuous problems, from diabetes to high blood pressure.
"The majority of children with this still go undiagnosed," said Dr. Jeffrey Schwimmer, head of the Fatty Liver Clinic at Rady Children's Hospital in San Diego. "Some kids have died."
The number of patients at his clinic has roughly tripled over its six years, and he's seen one with cirrhosis just 8 years old.
"Many of these children, their parents have it (fatty liver disease) and don't know it," said Schwimmer.
Experts say the best way to combat the problem is to intervene early, while it can still be reversed, with a medical team working with the whole family, including liver and hormone specialists, a dietitian and counselors.
Last spring, the American Academy of Pediatrics recommended doctors do a blood test of liver enzymes every two years on obese children and overweight ones with high blood pressure or cholesterol or family history of heart disease. A trade group for children's hospitals last year gave similar advice.
Within the last several months, there's been an explosion of research published on it and the role genes may play.
Surprisingly, some research comes from countries not known for high obesity rates: China, India and Iran. More reports come from Australia, England, Greece, Ireland, Israel, Italy and Japan. Doctors say globalization has given even poor countries fast food chains and sedentary pastimes: TV, Internet, video games.
Scientists now are seeking the best ways to treat it.
A small study in Rome showed weight loss helped. The U.S. government is testing the diabetes drug metformin and vitamin E and is funding about 20 other studies, including one that aims to determine how the disease progresses and who is most likely to develop cirrhosis or liver failure.
When her son was diagnosed with advanced liver disease three years ago, Susan Siegfried recalls being "devastated." Curtis, then 12, was just over 5-feet-5 and weighed 179 pounds. About 40 percent of his liver was scarred.
Her husband, Mike, decreed the whole family would change its diet, and all high-fat and junk food was removed from their home in Chester, Ill.
Susan Siegfried said her son went from being the "sit-in-front-of-the-TV, play-video-games kind of kid," tired and sickly, to full of energy and very active. He now bales hay and does other chores on his uncles' nearby farm. Initially, he dropped about 20 pounds. He's shot up 4 inches but only gained 8 pounds in the past two years.
A new liver biopsy last fall showed huge improvement in his liver.
"I'm definitely a lot thinner than I would have been if I hadn't done anything," said Curtis, who found exercising and cutting out sugar and fat wasn't that hard. "If you stick with it, you'll get used to it."
By LINDA A. JOHNSON
08 sept 2008--In a new and disturbing twist on the obesity epidemic, some overweight teenagers have severe liver damage caused by too much body fat, and a handful have needed liver transplants.
Many more may need a new liver by their 30s or 40s, say experts warning that pediatricians need to be more vigilant. The condition, which can lead to cirrhosis and liver failure or liver cancer, is being seen in kids in the United States, Europe, Australia and even some developing countries, according to a surge of recent medical studies and doctors interviewed by The Associated Press.
The American Liver Foundation and other experts estimate 2 percent to 5 percent of American children over age 5, nearly all of them obese or overweight, have the condition, called nonalcoholic fatty liver disease.
"It's clearly the most common cause of liver disease," said Dr. Ronald Sokol, head of public policy at the liver foundation and a liver specialist at Children's Hospital and University of Colorado Denver.
Some experts think as many as 10 percent of all children and half of those who are obese may suffer from it, but note that few are given the simple blood test that can signal its presence. A biopsy is the only sure way to diagnose this disease.
As fat builds up, the liver can become inflamed and then scarred over time, leading to cirrhosis, a serious condition, which in years past was mostly caused by hepatitis or drinking too much alcohol. Liver failure or liver cancer can follow, but if cirrhosis has not yet developed, fatty liver disease can be reversed through weight loss.
The disease is most common in overweight children with belly fat and certain warning signs, such as diabetes or cholesterol or heart problems. However, it's been seen in a few children of normal weight.
Genetics, diet and exercise level all play a role. It is most prevalent among Hispanics, relatively rare among African-Americans, and more common among boys than girls.
"There are people in their 30s or early 40s that will require a liver transplant" from developing the condition as a kid, predicts Dr. Jose Derdoy, head of liver transplants at Cardinal Glennon Children's Medical Center in St. Louis. He's treated a 15-year-old, 530-pound boy and many others with the condition.
Experts blame obesity, with about two-thirds of all Americans overweight. With fatty liver disease becoming more common in adults, many experts predict it will become the top cause of liver transplants by 2020.
"There aren't enough livers to go around," says Dr. Philip Rosenthal of the University of California-San Francisco Children's Hospital.
His patient, Irving Shaffino, a 15-year-old Mexican-American who lives outside Lubbock, Texas, was lucky to get a transplant a year ago. He was in end-stage cirrhosis and, at 5-feet-4 1/2, weighed 180 pounds.
Irving had been fat since age 6, thanks to a high-starch, high-fat diet of Mexican food, pizza and burgers, said his mother, Guadelupe Shaffino. At age 8, she said, he had a distended stomach and by his early teens, breathing problems kept him tethered to an oxygen tank at home.
Without health insurance, the family couldn't find a local hospital that would do a transplant.
"My son begged me, 'Don't let me die, Mommy,' so I did everything in my power to find a place to help him. Thanks be to God, we found a way," said Guadelupe Shaffino, a restaurant cook.
UCSF Children's Hospital, with money from a state health program, agreed to do the transplant. Rosenthal, who oversees the hospital's pediatric liver transplant program, took over care of Irving. The doctor said without a new liver Irving would have died, maybe within months.
"He was in bad shape," said Rosenthal.
Soon after tests were completed and Irving got on a transplant waiting list, an organ was found.
"It felt like a miracle, because people say you could be on the transplant list for years," Irving said.
Within a couple of months of the July 26, 2007 operation, Irving had weaned himself from the oxygen tank and could go on walks, although he got winded quickly.
Back home in Texas, his medications are down from 11 to four and Irving said he's replaced soda and fast food with fruit, vegetables and whole grains.
"I want to get into sports again," he said. "I want to get down to maybe 150" pounds.
Sadly, however, Irving has made little progress in losing weight. While he's grown an inch and a half since his operation, he's still obese and his weight was up to 219 last month.
Specialists say many kids diagnosed with fatty liver disease come to subsequent checkups heavier, and at best, just one in four loses significant weight, the only treatment known to stop and even reverse the disease.
"My patients that are successful, the whole family has bought in," increasing exercise and changing diet, said Dr. Stephanie Abrams, a liver and obesity specialist at Texas Children's Hospital. "The problem is that we aren't changing society in favor of becoming lean."
The scope of the disease has only been realized in recent years. Just a handful of cases were reported in medical journals in the 1980s, and in the past, many adult patients were thought to be lying when they denied drinking alcohol.
Only three liver transplants on American children with nonalcoholic fatty liver disease were recorded from 1990 through 2002; two were done last year.
"It really has been only in the last two or three years that this has become more commonplace," said Dr. Ann Scheimann, a pediatric gastroenterologist at Johns Hopkins Children's Center. "It is scary."
Like heart disease, liver disease is silent. Kids may feel fine for years. Any early symptoms, like fatigue and loss of appetite, are vague and usually eclipsed by more conspicuous problems, from diabetes to high blood pressure.
"The majority of children with this still go undiagnosed," said Dr. Jeffrey Schwimmer, head of the Fatty Liver Clinic at Rady Children's Hospital in San Diego. "Some kids have died."
The number of patients at his clinic has roughly tripled over its six years, and he's seen one with cirrhosis just 8 years old.
"Many of these children, their parents have it (fatty liver disease) and don't know it," said Schwimmer.
Experts say the best way to combat the problem is to intervene early, while it can still be reversed, with a medical team working with the whole family, including liver and hormone specialists, a dietitian and counselors.
Last spring, the American Academy of Pediatrics recommended doctors do a blood test of liver enzymes every two years on obese children and overweight ones with high blood pressure or cholesterol or family history of heart disease. A trade group for children's hospitals last year gave similar advice.
Within the last several months, there's been an explosion of research published on it and the role genes may play.
Surprisingly, some research comes from countries not known for high obesity rates: China, India and Iran. More reports come from Australia, England, Greece, Ireland, Israel, Italy and Japan. Doctors say globalization has given even poor countries fast food chains and sedentary pastimes: TV, Internet, video games.
Scientists now are seeking the best ways to treat it.
A small study in Rome showed weight loss helped. The U.S. government is testing the diabetes drug metformin and vitamin E and is funding about 20 other studies, including one that aims to determine how the disease progresses and who is most likely to develop cirrhosis or liver failure.
When her son was diagnosed with advanced liver disease three years ago, Susan Siegfried recalls being "devastated." Curtis, then 12, was just over 5-feet-5 and weighed 179 pounds. About 40 percent of his liver was scarred.
Her husband, Mike, decreed the whole family would change its diet, and all high-fat and junk food was removed from their home in Chester, Ill.
Susan Siegfried said her son went from being the "sit-in-front-of-the-TV, play-video-games kind of kid," tired and sickly, to full of energy and very active. He now bales hay and does other chores on his uncles' nearby farm. Initially, he dropped about 20 pounds. He's shot up 4 inches but only gained 8 pounds in the past two years.
A new liver biopsy last fall showed huge improvement in his liver.
"I'm definitely a lot thinner than I would have been if I hadn't done anything," said Curtis, who found exercising and cutting out sugar and fat wasn't that hard. "If you stick with it, you'll get used to it."
Sunday, September 07, 2008
Pfizer and Medivation Enter into Global Agreement to Co-Develop and Market Dimebon for the Treatment of Alzheimer’s Disease
NEW YORK , 07 sept 2008--Pfizer Inc and Medivation, Inc. announced today that they have entered into an agreement to develop and commercialize Dimebon, Medivation’s investigational drug for treatment of Alzheimer’s disease and Huntington’s disease. Dimebon currently is being evaluated in an international, confirmatory Phase III trial in patients with mild-to-moderate Alzheimer’s disease (http://www.connectionstudy.com/).
Under the terms of the agreement, Medivation will receive an up-front cash payment of $225 million. Medivation also is eligible to receive payments of up to $500 million upon the attainment of development and regulatory milestones plus additional undisclosed commercial milestone payments. Medivation and Pfizer will collaborate on the Phase III program in Alzheimer’s disease, Huntington’s disease development and regulatory filings in the United States. The companies will share all U.S. development and commercialization expenses along with U.S. profits/losses on a 60 percent/40 percent basis, with Pfizer assuming the larger share of both expenses and profit/losses. In addition, Medivation will co-promote Dimebon to specialty physicians in the U.S.
Pfizer will have responsibility for development, regulatory and commercialization outside the U.S. and will pay Medivation tiered royalties on commercial sales outside of the U.S. The agreement is subject to approval under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. J.P. Morgan served as financial advisor, and Cooley Godward Kronish LLP served as legal advisor, to Medivation on this transaction.
Alzheimer’s disease leads to the death of brain cells and the loss of nerve connections in areas of the brain that govern memory, thinking and behavior. Alzheimer’s disease gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate and carry-out daily activities. No currently marketed Alzheimer’s disease drug appears to stop brain cell death and prevent or restore lost nerve connections.
Dimebon is an orally-available, small molecule that has been shown to inhibit brain cell death in preclinical models relevant to Alzheimer’s disease and Huntington’s disease, making it a potential treatment for these and other neurodegenerative conditions. Based on preclinical data generated to date, Dimebon appears to improve the function of mitochondria, the energy generators in cells that play a vital role in governing brain cell health, growth and overall function. Dimebon also has been shown to stimulate the outgrowth of nerves from brain cells, or neurites, a process that is believed to play an important role in restoring or generating new brain cell connections.
“With more than 18 million people worldwide suffering from the debilitating and ultimately fatal effects of Alzheimer’s disease, Pfizer has made this devastating illness one of our highest priorities,” said Dr. Martin Mackay, president, Pfizer Global Research and Development. “We are working to develop new medicines that improve memory and halt or significantly slow the disease’s progression. We look forward to collaborating with Medivation to bring Dimebon to patients as rapidly as possible.”
“After a rigorous process that garnered substantial interest, we believe that Pfizer is the ideal partner, sharing our vision for Dimebon and capable of maximizing its potential globally," said Dr. David Hung, president and chief executive officer of Medivation. "As one of the leaders in Alzheimer’s disease, Pfizer is an optimal partner because of its extensive experience developing new medicines; its marketing and commercialization track record; and, its significant global capability to effectively reach primary care physicians, who today prescribe the vast majority of Alzheimer’s disease medications in the U.S.”
About Dimebon’s Clinical Program
Results from the first pivotal trial of Dimebon in Alzheimer’s disease showed that patients treated with Dimebon experienced statistically significant improvements compared to placebo in key aspects of the disease -- memory and thinking, activities of daily living, behavior and overall function. Dimebon’s benefit over placebo continued to increase throughout the 12-month treatment period. At the end of 12 months, Dimebon-treated patients were on average functioning as well or better than they had been at the start of the study on each of 5 clinical endpoints. These results were published in the July 19, 2008 issue of The Lancet, and are noteworthy as untreated Alzheimer's patients progressively deteriorate over time in these areas.
ESC: Statin Therapy Reduces Perioperative Cardiac Events
By Ed Susman
MUNICH, 07 sept 2008-- Extended-release fluvastatin (Lescol) -- given to patients just before undergoing vascular surgery and continued for a month -- reduced the relative risk of suffering a heart attack by a significant 47%, Dutch researchers reported here. "Perioperative extended-release fluvastatin use might be recommended in vascular surgery patients," suggested Don Poldermans, M.D., of Erasmus University in Rotterdam, at the European Society of Cardiology meeting. Treatment was started at the outpatient clinic on the day of randomization, a median 37 days prior to the surgical procedure, and was continued at least during the first 30 days after surgery. The primary analysis was intention-to-treat and involved all patients who were randomly assigned to either fluvastatin or placebo. Directly after surgery, study treatment was temporarily discontinued in 115 (23%) patients for a median duration of two days because of the inability to take the study drug orally.
A total of 34 patients discontinued the study medication because of laboratory abnormalities, 16 (3.2%) because of alanine aminotransferase exceeding three times the upper limit of normal, 13 (2.6%) because of creatinine kinase exceeding 10 times theupper limit of normal, and five (1%) because of a combination of elevated alanine aminotransferase and CK.
Dr. Poldermans said that myocardial ischemia occurred in 10.6% of the 250 patients assigned to fluvastatin compared with 18.2% of the 247 patients who were randomly assigned to receive placebo in the study (OR 0.53, 95% CI 0.32 to 0.88, P=0.016). The number needed to treat to prevent one patient experiencing myocardial ischemia was 12.5 patients.
In addition, he said that after 30 days of the trial period, 12 (4.8%) of the patients on fluvastatin achieved the secondary endpoint of cardiovascular death and/or nonfatal myocardial infarction compared with 25 (10.1%) of patients on placebo (OR 0.48, 95% CI 0.24 to 0.95, P=0.039).
In reporting the results of the Dutch Echographic Cardiac Risk Evaluating Applying Stress Echo III (DECREASE) trial, Dr. Poldermans noted that the use of 80 mg of extended-release fluvastatin in the patients just prior to surgery and until 30 days after the vascular surgery was not accompanied by an increase in adverse side effects, liver dysfunction, or myopathy compared with placebo.
"This therapy was associated with improved postoperative cardiac outcome in high-risk patients undergoing elective vascular surgery," he said.
"The results of DECREASE are a good demonstration of the benefits of statins beyond their ability to reduce cholesterol," commented Timothy Gardner, M.D., director of the Heart and Valvular Institute for Christiana Care, Wilmington, Del., and president of the American Heart Association. He said the patients were undergoing aortic surgery or peripheral vascular surgery.
Dr. Gardner said fluvastatin is not used widely in the United States so he anticipated that other companies that make statins were likely to attempt to replicate the results of DECREASE.
Dr. Poldermans said his group employed fluvastatin in the trial not to reduce cholesterol, but to make use of the purported pleiotropic effects of statins -- in particular the drugs' known ability to reduce inflammatory responses that occur in surgical scenarios.
He noted that about 2% of patients undergoing noncardiac vascular surgery die from cardiac causes during the perioperative period. He said that causes of perioperative myocardial infarction are complex but one theory suggests that coronary plaque instability leading to plaque rupture and thrombosis is a significant problem. He said the trial aimed at assessing the cardioprotective effect of fluvastatin on top of beta-blocker therapy in vascular surgery patients.
"What we have learned from the DECREASE study," said Elliot Antman, M.D., of Harvard Medical School, Boston, and another spokesperson for the American Heart Association, "is that there may be additional medical benefits of starting the statins early."
Neither Dr. Gardner nor Dr. Poldermans had any disclosures. Dr. Antman disclosed relationships with Merck & Co., Inc., Bristol-Myers Squibb Pharmaceutical Research Institute, sanofi-aventis, Millennium Pharmaceuticals, Nuvelo Inc., AstraZenaca Pharmaceuticals LP, CV Therapeutics, Inotek Pharmaceuticals Corporation, Eli Lilly and Company, Schering-Plough Research Institute, Integrated Therapeutics Corporation, Bayer Healthcare LLC, Ortho-Clinical Diagnostics, Inc., Sanofi-Synthelabo Recherche, GlaxoSmithKline, Amgen Inc., Beckman Coulter, Inc., Biosite Incorporated, Roche Diagnostics Corporation, Roche Diagnostics GmbH, Pfizer, Inc., Accumetrics, Inc., the National Institutes of Health, and Novartis Pharmaceuticals.
Primary source: European Society of CardiologySource reference:Poldermans D, et al "Fluvastatin XL use is associated with improved cardiac outcome after major vascular surgery: Results form a randomizxed placebo controlled trial" ESC 2008.
By Ed Susman
MUNICH, 07 sept 2008-- Extended-release fluvastatin (Lescol) -- given to patients just before undergoing vascular surgery and continued for a month -- reduced the relative risk of suffering a heart attack by a significant 47%, Dutch researchers reported here. "Perioperative extended-release fluvastatin use might be recommended in vascular surgery patients," suggested Don Poldermans, M.D., of Erasmus University in Rotterdam, at the European Society of Cardiology meeting. Treatment was started at the outpatient clinic on the day of randomization, a median 37 days prior to the surgical procedure, and was continued at least during the first 30 days after surgery. The primary analysis was intention-to-treat and involved all patients who were randomly assigned to either fluvastatin or placebo. Directly after surgery, study treatment was temporarily discontinued in 115 (23%) patients for a median duration of two days because of the inability to take the study drug orally.
A total of 34 patients discontinued the study medication because of laboratory abnormalities, 16 (3.2%) because of alanine aminotransferase exceeding three times the upper limit of normal, 13 (2.6%) because of creatinine kinase exceeding 10 times theupper limit of normal, and five (1%) because of a combination of elevated alanine aminotransferase and CK.
Dr. Poldermans said that myocardial ischemia occurred in 10.6% of the 250 patients assigned to fluvastatin compared with 18.2% of the 247 patients who were randomly assigned to receive placebo in the study (OR 0.53, 95% CI 0.32 to 0.88, P=0.016). The number needed to treat to prevent one patient experiencing myocardial ischemia was 12.5 patients.
In addition, he said that after 30 days of the trial period, 12 (4.8%) of the patients on fluvastatin achieved the secondary endpoint of cardiovascular death and/or nonfatal myocardial infarction compared with 25 (10.1%) of patients on placebo (OR 0.48, 95% CI 0.24 to 0.95, P=0.039).
In reporting the results of the Dutch Echographic Cardiac Risk Evaluating Applying Stress Echo III (DECREASE) trial, Dr. Poldermans noted that the use of 80 mg of extended-release fluvastatin in the patients just prior to surgery and until 30 days after the vascular surgery was not accompanied by an increase in adverse side effects, liver dysfunction, or myopathy compared with placebo.
"This therapy was associated with improved postoperative cardiac outcome in high-risk patients undergoing elective vascular surgery," he said.
"The results of DECREASE are a good demonstration of the benefits of statins beyond their ability to reduce cholesterol," commented Timothy Gardner, M.D., director of the Heart and Valvular Institute for Christiana Care, Wilmington, Del., and president of the American Heart Association. He said the patients were undergoing aortic surgery or peripheral vascular surgery.
Dr. Gardner said fluvastatin is not used widely in the United States so he anticipated that other companies that make statins were likely to attempt to replicate the results of DECREASE.
Dr. Poldermans said his group employed fluvastatin in the trial not to reduce cholesterol, but to make use of the purported pleiotropic effects of statins -- in particular the drugs' known ability to reduce inflammatory responses that occur in surgical scenarios.
He noted that about 2% of patients undergoing noncardiac vascular surgery die from cardiac causes during the perioperative period. He said that causes of perioperative myocardial infarction are complex but one theory suggests that coronary plaque instability leading to plaque rupture and thrombosis is a significant problem. He said the trial aimed at assessing the cardioprotective effect of fluvastatin on top of beta-blocker therapy in vascular surgery patients.
"What we have learned from the DECREASE study," said Elliot Antman, M.D., of Harvard Medical School, Boston, and another spokesperson for the American Heart Association, "is that there may be additional medical benefits of starting the statins early."
Neither Dr. Gardner nor Dr. Poldermans had any disclosures. Dr. Antman disclosed relationships with Merck & Co., Inc., Bristol-Myers Squibb Pharmaceutical Research Institute, sanofi-aventis, Millennium Pharmaceuticals, Nuvelo Inc., AstraZenaca Pharmaceuticals LP, CV Therapeutics, Inotek Pharmaceuticals Corporation, Eli Lilly and Company, Schering-Plough Research Institute, Integrated Therapeutics Corporation, Bayer Healthcare LLC, Ortho-Clinical Diagnostics, Inc., Sanofi-Synthelabo Recherche, GlaxoSmithKline, Amgen Inc., Beckman Coulter, Inc., Biosite Incorporated, Roche Diagnostics Corporation, Roche Diagnostics GmbH, Pfizer, Inc., Accumetrics, Inc., the National Institutes of Health, and Novartis Pharmaceuticals.
Primary source: European Society of CardiologySource reference:Poldermans D, et al "Fluvastatin XL use is associated with improved cardiac outcome after major vascular surgery: Results form a randomizxed placebo controlled trial" ESC 2008.
FDA: Manufacturers of TNF-Blocker Drugs Must Highlight Risk of Fungal Infections
Agency invokes new authorities under FDAAA to alert patients and prescribers to risk
07 spt 2008--The U.S. Food and Drug Administration today announced that the manufacturers of Humira, Cimzia, Enbrel, and Remicade must strengthen the existing warnings, in the Warnings and Precaution sections of the drugs' prescribing information and Medication Guides, on the risk of developing opportunistic fungal infections. Some patients with invasive fungal infections have died.
The four drugs, known as tumor necrosis factor alpha blockers (TNF-alpha blockers), which suppress the immune system, are approved to treat a variety of conditions which may include rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and Crohn's disease.
FDA today exercised its new authority under the Food and Drug Administration Amendments Act of 2007 to require manufacturers of TNF inhibitors to make safety-related changes to prescribing information, or labeling.
“Under the FDA's new authorities, we can require safety label changes and a risk evaluation and mitigation strategy, known as REMS, when the agency becomes aware of new safety information,” said Bob Rappaport, M.D., director of the Division of Anesthesia, Analgesia and Rheumatology Products, Center for Drug Evaluation and Research. “Requiring the risks to be highlighted will help health care professionals be more vigilant in watching for these adverse events, and is necessary to ensure that the benefits of these drugs outweigh their risks.”
Since the initial approval of the four TNF blockers, the prescribing information for these drugs has included information about the risk of serious infections, including fungal infections. However, based on reports reviewed by FDA, health care professionals are not consistently recognizing cases of histoplasmosis and other invasive fungal infections, leading to delays in treatment.
Patients taking TNF blockers should be aware that they are more susceptible to serious fungal infections. Those who develop a persistent fever, cough, shortness of breath, and fatigue should promptly seek medical attention. To assist in the diagnosis, those being treated with TNF blockers should tell their health care professionals where they live and what areas they have recently visited. Patients who develop a fungal infection may be advised to stop the TNF blocker until they recover.
FDA has reviewed 240 reports of histoplasmosis, an infection caused by the fungusHistoplasma capsulatum, in patients being treated with Enbrel, Humira, or Remicade. The majority of the reports involved people in the Ohio River and Mississippi River valleys (the fungus is commonly found in those areas). In at least 21 of the reports, histoplasmosis was initially not recognized by health care professionals, and antifungal treatment was delayed. Twelve of those patients died.
The FDA reviewed one reported case of histoplasmosis in a patient taking Cimzia. The FDA also has received reports of cases of coccidioidomycosis and blastomycosis, including deaths, in patients treated with TNF blockers.
TNF blocker manufacturers are required to submit safety labeling changes, including strengthened warnings and revisions to the Medication Guides to the FDA within 30 days or to provide a reason why they do not believe labeling changes are necessary.
If they do not submit new language, or if the FDA disagrees with the new language the company proposes, the Food and Drug Administration Amendments Act of 2007 provides strict timelines for resolving the labeling changes and allows the agency to issue an order directing the labeling change as deemed appropriate to address the new safety information.
Medication Guides will become part of a REMS for Humira and Remicade and are already part of a REMS for Enbrel and Cimzia. The manufacturers for all four of these drugs will also be required to educate prescribers about the risks.
For more information: http://www.fda.gov/cder/drug/InfoSheets/HCP/TNF_blockersHCP.htm
Agency invokes new authorities under FDAAA to alert patients and prescribers to risk
07 spt 2008--The U.S. Food and Drug Administration today announced that the manufacturers of Humira, Cimzia, Enbrel, and Remicade must strengthen the existing warnings, in the Warnings and Precaution sections of the drugs' prescribing information and Medication Guides, on the risk of developing opportunistic fungal infections. Some patients with invasive fungal infections have died.
The four drugs, known as tumor necrosis factor alpha blockers (TNF-alpha blockers), which suppress the immune system, are approved to treat a variety of conditions which may include rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and Crohn's disease.
FDA today exercised its new authority under the Food and Drug Administration Amendments Act of 2007 to require manufacturers of TNF inhibitors to make safety-related changes to prescribing information, or labeling.
“Under the FDA's new authorities, we can require safety label changes and a risk evaluation and mitigation strategy, known as REMS, when the agency becomes aware of new safety information,” said Bob Rappaport, M.D., director of the Division of Anesthesia, Analgesia and Rheumatology Products, Center for Drug Evaluation and Research. “Requiring the risks to be highlighted will help health care professionals be more vigilant in watching for these adverse events, and is necessary to ensure that the benefits of these drugs outweigh their risks.”
Since the initial approval of the four TNF blockers, the prescribing information for these drugs has included information about the risk of serious infections, including fungal infections. However, based on reports reviewed by FDA, health care professionals are not consistently recognizing cases of histoplasmosis and other invasive fungal infections, leading to delays in treatment.
Patients taking TNF blockers should be aware that they are more susceptible to serious fungal infections. Those who develop a persistent fever, cough, shortness of breath, and fatigue should promptly seek medical attention. To assist in the diagnosis, those being treated with TNF blockers should tell their health care professionals where they live and what areas they have recently visited. Patients who develop a fungal infection may be advised to stop the TNF blocker until they recover.
FDA has reviewed 240 reports of histoplasmosis, an infection caused by the fungusHistoplasma capsulatum, in patients being treated with Enbrel, Humira, or Remicade. The majority of the reports involved people in the Ohio River and Mississippi River valleys (the fungus is commonly found in those areas). In at least 21 of the reports, histoplasmosis was initially not recognized by health care professionals, and antifungal treatment was delayed. Twelve of those patients died.
The FDA reviewed one reported case of histoplasmosis in a patient taking Cimzia. The FDA also has received reports of cases of coccidioidomycosis and blastomycosis, including deaths, in patients treated with TNF blockers.
TNF blocker manufacturers are required to submit safety labeling changes, including strengthened warnings and revisions to the Medication Guides to the FDA within 30 days or to provide a reason why they do not believe labeling changes are necessary.
If they do not submit new language, or if the FDA disagrees with the new language the company proposes, the Food and Drug Administration Amendments Act of 2007 provides strict timelines for resolving the labeling changes and allows the agency to issue an order directing the labeling change as deemed appropriate to address the new safety information.
Medication Guides will become part of a REMS for Humira and Remicade and are already part of a REMS for Enbrel and Cimzia. The manufacturers for all four of these drugs will also be required to educate prescribers about the risks.
For more information: http://www.fda.gov/cder/drug/InfoSheets/HCP/TNF_blockersHCP.htm
Study: No proof Vytorin linked to cancer; other doctors warn it should be used carefully
By MARIA CHENG
MUNICH, Germany, 07 sept 2008 - Results so far from three studies of the cholesterol-lowering drug Vytorin are not enough to prove or rule out a possible link to a higher risk of cancer, so the drug should be used with caution until more is known, editors of a leading medical journal urged Tuesday.
The New England Journal of Medicine published results online from one study and an analysis of partial results from two others. They also were presented at a cardiology conference in Munich.
Vytorin is a combination of Merck's Zocor, a long-sold statin drug, and Schering-Plough's Zetia, a newer type of medicine that lowers cholesterol in a different way.
The possible cancer risk unexpectedly arose in July, when Dr. Terje Pedersen of Oslo, Norway, announced preliminary results from a study testing whether Vytorin could prevent damage to the heart's aortic valve from worsening.
The drug made no difference in heart attacks, strokes or surgeries related to the valve problem. But doctors saw a greater number of cancer cases in those taking it compared to others given dummy pills.
That prompted an interim analysis of results of two other ongoing studies of Vytorin by scientists at Oxford University in England. Their review found higher rates of cancer deaths among Vytorin users, but the number of cancer cases did not significantly differ.
"I don't think there is any evidence of hazard here," concluded Sir Richard Peto, a cancer epidemiologist who is helping lead one of the drug company-sponsored studies.
But editors of the medical journal noted that participants in these two studies have been followed for less than three years — a short time for risks like cancer to emerge — and concluded that a link could not be ruled out. Patients and doctors "are unfortunately left for now with uncertainty" about the safety and effectiveness of the drug, they wrote.
Other doctors also were not convinced that Vytorin is safe.
"The jury is still out as to whether there's a cancer signal," said Dr. Gordon Tomaselli, cardiology chief at Johns Hopkins Hospital and a spokesman for the American Heart Association. He was not connected to the research.
Pedersen's study involved 1,873 people in Europe and the United States who were starting to have problems with their aortic valves. They were either given Vytorin or a placebo in hopes that lowering cholesterol would ward off future heart problems.
Of those given Vytorin, 105 developed cancer, compared with 70 among those on placebo. That is higher than the 93 cases among Vytorin users and 65 in the others that scientists reported on a conference call in July when the issue first became known.
Cancer-related deaths were higher in all three studies. Editors of the medical journal, who combined the results and found 134 among Vytorin users and 92 in the others, said the increase cannot simply be chalked up to chance.
Some doctors said that although Vytorin may not have helped heart valve problems, it still might be useful for people who need their cholesterol lowered — if other drugs do not work.
"If I was on this medication and it was the only way to get my cholesterol down, I would not change my therapy based on this," said Dr. Douglas Weaver, president of the American College of Cardiology. The group has been asked by the U.S. Senate to account for the money it accepts from pharmaceutical companies, including Merck. The American Heart Association also accepts funding from Merck and other drug companies to finance ongoing operations.
The federal Food and Drug Administration is looking into the cancer concerns but has said that patients should not stop taking Vytorin because the evidence of any link is unclear.
With other options available for heart patients, some doctors said there was no obvious reason to take Vytorin. "There's no proof that this combination is working," said Dr. Christer Hoglund, a cardiologist at Sweden's Karolinska Institute.
"We don't know that this drug is bad, but we don't know that it's any good either."
By MARIA CHENG
MUNICH, Germany, 07 sept 2008 - Results so far from three studies of the cholesterol-lowering drug Vytorin are not enough to prove or rule out a possible link to a higher risk of cancer, so the drug should be used with caution until more is known, editors of a leading medical journal urged Tuesday.
The New England Journal of Medicine published results online from one study and an analysis of partial results from two others. They also were presented at a cardiology conference in Munich.
Vytorin is a combination of Merck's Zocor, a long-sold statin drug, and Schering-Plough's Zetia, a newer type of medicine that lowers cholesterol in a different way.
The possible cancer risk unexpectedly arose in July, when Dr. Terje Pedersen of Oslo, Norway, announced preliminary results from a study testing whether Vytorin could prevent damage to the heart's aortic valve from worsening.
The drug made no difference in heart attacks, strokes or surgeries related to the valve problem. But doctors saw a greater number of cancer cases in those taking it compared to others given dummy pills.
That prompted an interim analysis of results of two other ongoing studies of Vytorin by scientists at Oxford University in England. Their review found higher rates of cancer deaths among Vytorin users, but the number of cancer cases did not significantly differ.
"I don't think there is any evidence of hazard here," concluded Sir Richard Peto, a cancer epidemiologist who is helping lead one of the drug company-sponsored studies.
But editors of the medical journal noted that participants in these two studies have been followed for less than three years — a short time for risks like cancer to emerge — and concluded that a link could not be ruled out. Patients and doctors "are unfortunately left for now with uncertainty" about the safety and effectiveness of the drug, they wrote.
Other doctors also were not convinced that Vytorin is safe.
"The jury is still out as to whether there's a cancer signal," said Dr. Gordon Tomaselli, cardiology chief at Johns Hopkins Hospital and a spokesman for the American Heart Association. He was not connected to the research.
Pedersen's study involved 1,873 people in Europe and the United States who were starting to have problems with their aortic valves. They were either given Vytorin or a placebo in hopes that lowering cholesterol would ward off future heart problems.
Of those given Vytorin, 105 developed cancer, compared with 70 among those on placebo. That is higher than the 93 cases among Vytorin users and 65 in the others that scientists reported on a conference call in July when the issue first became known.
Cancer-related deaths were higher in all three studies. Editors of the medical journal, who combined the results and found 134 among Vytorin users and 92 in the others, said the increase cannot simply be chalked up to chance.
Some doctors said that although Vytorin may not have helped heart valve problems, it still might be useful for people who need their cholesterol lowered — if other drugs do not work.
"If I was on this medication and it was the only way to get my cholesterol down, I would not change my therapy based on this," said Dr. Douglas Weaver, president of the American College of Cardiology. The group has been asked by the U.S. Senate to account for the money it accepts from pharmaceutical companies, including Merck. The American Heart Association also accepts funding from Merck and other drug companies to finance ongoing operations.
The federal Food and Drug Administration is looking into the cancer concerns but has said that patients should not stop taking Vytorin because the evidence of any link is unclear.
With other options available for heart patients, some doctors said there was no obvious reason to take Vytorin. "There's no proof that this combination is working," said Dr. Christer Hoglund, a cardiologist at Sweden's Karolinska Institute.
"We don't know that this drug is bad, but we don't know that it's any good either."
Study says bypass surgery for heart patients better than stents in the long term
By MARIA CHENG
MUNICH, Germany, 07 sept 2008 - For heart patients with clogged arteries, the choice between bypass surgery or an angioplasty may come down to one question: How many procedures would you like to have?
In research presented Monday at the European Society of Cardiology meeting in Munich, experts concluded that while bypass surgery and angioplasty offer comparable results, patients who have angioplasties are twice as likely to require another procedure within a year.
"If you don't want to have another heart operation for at least a decade, you should pick the surgery," said Dr. Heinz Drexel, professor of medicine at the University of Innsbruck in Austria and spokesman for the European Society of Cardiology. Drexel was not connected to the research.
"But that means you have to have your chest cracked open," he said.
When arteries become blocked, doctors have two main options. Traditionally they have done a bypass surgery, which reroutes blood vessels to detour around blockages.
But in recent years, angioplasties have become increasingly popular. An angioplasty is a non-surgical procedure where a balloon is pushed into a blood vessel to flatten the blockage, leaving a stent to prop the artery open.
In the study results announced Monday, European doctors compared the effectiveness of open-heart surgery versus angioplasty in a trial of more than 3,000 patients in Europe and the United States. They excluded patients who had acute heart attacks and included those who had single and multiple vessel blockages.
About a third of the patients had medical conditions that required surgery. The remaining patients were randomly assigned to receive either surgery or an angioplasty. Patients who got an angioplasty needed an average of nearly five stents.
The study was paid for by Boston Scientific, makers of the drug-coated stent used in the trial.
After one year, researchers found that patients who had surgery had a lower death rate. Among surgery patients, the death rate was 3.5 percent; in angioplasty patients, it was 4.3 percent.
In patients who had an angioplasty, nearly 14 percent needed another procedure after a year, compared with about 6 percent of surgery patients.
But patients who had surgery had about a 2 percent stroke risk versus nearly zero risk for patients who had an angioplasty. Doctors said that any surgery had an inherent stroke risk, compared with an angioplasty.
In January, a study published in the New England Journal of Medicine found that bypass surgery was still the best option for heart patients with more than one clogged artery.
"Surgery still comes out as the winner in a head-to-head trial," said Dr. Douglas Weaver, president of the American College of Cardiology, who was unconnected to the research.
"This comes down to a conversation with patients and making sure they know that with an angioplasty, there will be a higher rate of revascularization," he said, referring to the need for repeat procedures.
Patients typically need at least a month to fully recover from an open-heart surgery, a five-hour long operation under general anesthesia.
Angioplasty patients, however, are often up and walking around after three days.
"You invest more in terms of recuperation with surgery," said Dr. Tim Gardner, president of the American Heart Association. "But the advantage is durability."
When drug-coated stents were first introduced in 2003, they became the fastest-selling medical device in recent history. Doctors thought that the tiny tubes, which leak drugs to prevent tissue regrowth, would make angioplasty a much better alternative to surgery for patients.
But in 2006, studies began to emerge showing that patients with the drug-coated stents were more likely to develop potentially fatal blood clots months and even years after they were implanted.
Stent sales plummeted and doctors have become more wary of their use, saving them only for certain patients with no other options.
Doctors cautioned that more data is still needed about the pros and cons of bypass surgery versus angioplasties, and that patients needed to be tracked for at least five years.
"This only tells us what happens after one year," Drexel said. "We need to wait for at least five years to get a good answer about which therapy is really better."
By MARIA CHENG
MUNICH, Germany, 07 sept 2008 - For heart patients with clogged arteries, the choice between bypass surgery or an angioplasty may come down to one question: How many procedures would you like to have?
In research presented Monday at the European Society of Cardiology meeting in Munich, experts concluded that while bypass surgery and angioplasty offer comparable results, patients who have angioplasties are twice as likely to require another procedure within a year.
"If you don't want to have another heart operation for at least a decade, you should pick the surgery," said Dr. Heinz Drexel, professor of medicine at the University of Innsbruck in Austria and spokesman for the European Society of Cardiology. Drexel was not connected to the research.
"But that means you have to have your chest cracked open," he said.
When arteries become blocked, doctors have two main options. Traditionally they have done a bypass surgery, which reroutes blood vessels to detour around blockages.
But in recent years, angioplasties have become increasingly popular. An angioplasty is a non-surgical procedure where a balloon is pushed into a blood vessel to flatten the blockage, leaving a stent to prop the artery open.
In the study results announced Monday, European doctors compared the effectiveness of open-heart surgery versus angioplasty in a trial of more than 3,000 patients in Europe and the United States. They excluded patients who had acute heart attacks and included those who had single and multiple vessel blockages.
About a third of the patients had medical conditions that required surgery. The remaining patients were randomly assigned to receive either surgery or an angioplasty. Patients who got an angioplasty needed an average of nearly five stents.
The study was paid for by Boston Scientific, makers of the drug-coated stent used in the trial.
After one year, researchers found that patients who had surgery had a lower death rate. Among surgery patients, the death rate was 3.5 percent; in angioplasty patients, it was 4.3 percent.
In patients who had an angioplasty, nearly 14 percent needed another procedure after a year, compared with about 6 percent of surgery patients.
But patients who had surgery had about a 2 percent stroke risk versus nearly zero risk for patients who had an angioplasty. Doctors said that any surgery had an inherent stroke risk, compared with an angioplasty.
In January, a study published in the New England Journal of Medicine found that bypass surgery was still the best option for heart patients with more than one clogged artery.
"Surgery still comes out as the winner in a head-to-head trial," said Dr. Douglas Weaver, president of the American College of Cardiology, who was unconnected to the research.
"This comes down to a conversation with patients and making sure they know that with an angioplasty, there will be a higher rate of revascularization," he said, referring to the need for repeat procedures.
Patients typically need at least a month to fully recover from an open-heart surgery, a five-hour long operation under general anesthesia.
Angioplasty patients, however, are often up and walking around after three days.
"You invest more in terms of recuperation with surgery," said Dr. Tim Gardner, president of the American Heart Association. "But the advantage is durability."
When drug-coated stents were first introduced in 2003, they became the fastest-selling medical device in recent history. Doctors thought that the tiny tubes, which leak drugs to prevent tissue regrowth, would make angioplasty a much better alternative to surgery for patients.
But in 2006, studies began to emerge showing that patients with the drug-coated stents were more likely to develop potentially fatal blood clots months and even years after they were implanted.
Stent sales plummeted and doctors have become more wary of their use, saving them only for certain patients with no other options.
Doctors cautioned that more data is still needed about the pros and cons of bypass surgery versus angioplasties, and that patients needed to be tracked for at least five years.
"This only tells us what happens after one year," Drexel said. "We need to wait for at least five years to get a good answer about which therapy is really better."
Saturday, September 06, 2008
For the Brain, Remembering Is Like Reliving
By BENEDICT CAREY
06 sept 2008--Scientists have for the first time recorded individual brain cells in the act of summoning a spontaneous memory, revealing not only where a remembered experience is registered but also, in part, how the brain is able to recreate it.
The recordings, taken from the brains of epilepsy patients being prepared for surgery, demonstrate that these spontaneous memories reside in some of the same neurons that fired most furiously when the recalled event had been experienced. Researchers had long theorized as much but until now had only indirect evidence.
Experts said the study had all but closed the case: For the brain, remembering is a lot like doing (at least in the short term, as the research says nothing about more distant memories).
The experiment, being reported Friday in the journal Science, is likely to open a new avenue in the investigation of Alzheimer’s disease and other forms of dementia, some experts said, as well as help explain how some memories seemingly come out of nowhere. The researchers were even able to identify specific memories in subjects a second or two before the people themselves reported having them.
“This is what I would call a foundational finding,” said Michael J. Kahana, a professor of psychology at the University of Pennsylvania, who was not involved in the research. “I cannot think of any recent study that’s comparable.
“It’s a really central piece of the memory puzzle and an important step in helping us fill in the detail of what exactly is happening when the brain performs this mental time travel” of summoning past experiences.
The new study moved beyond most previous memory research in that it focused not on recognition or recollection of specific symbols but on free recall — whatever popped into people’s heads when, in this case, they were asked to remember short film clips they had just seen.
This ability to richly reconstitute past experience often quickly deteriorates in people with Alzheimer’s and other forms of dementia, and it is fundamental to so-called episodic memory — the catalog of vignettes that together form our remembered past.
In the study, a team of American and Israeli researchers threaded tiny electrodes into the brains of 13 people with severe epilepsy. The electrode implants are standard procedure in such cases, allowing doctors to pinpoint the location of the mini-storms of brain activity that cause epileptic seizures.
The patients watched a series of 5- to 10-second film clips, some from popular television shows like “Seinfeld” and others depicting animals or landmarks like the Eiffel Tower. The researchers recorded the firing activity of about 100 neurons per person; the recorded neurons were concentrated in and around the hippocampus, a sliver of tissue deep in the brain known to be critical to forming memories.
In each person, the researchers identified single cells that became highly active during some videos and quiet during others. More than half the recorded cells hummed with activity in response to at least one film clip; many of them also responded weakly to others.
After briefly distracting the patients, the researchers then asked them to think about the clips for a minute and to report “what comes to mind.” The patients remembered almost all of the clips. And when they recalled a specific one — say, a clip of Homer Simpson — the same cells that had been active during the Homer clip reignited. In fact, the cells became active a second or two before people were conscious of the memory, which signaled to researchers the memory to come.
“It’s astounding to see this in a single trial; the phenomenon is strong, and we were listening in the right place,” said the senior author, Dr. Itzhak Fried, a professor of neurosurgery at the University of California, Los Angeles, and the University of Tel Aviv.
His co-authors were Hagar Gelbard-Sagiv, Michal Harel and Rafael Malach of the Weizmann Institute of Science in Israel, and Roy Mukamel, of U.C.L.A.
Dr. Fried said in a phone interview that the single neurons recorded firing most furiously during the film clips were not acting on their own; they were, like all such cells, part of a circuit responding to the videos, including thousands, perhaps millions, of other cells.
In studies of rodents, including a paper that will also appear Friday in the journal Science, neuroscientists have shown that special cells in the hippocampus are sensitive to location, activating when the animal passes a certain spot in a maze. The firing pattern of these cells forms the animals’ spatial memory and can predict which way the animal will turn, even if it makes a wrong move.
Some scientists argue that as humans evolved, these same cells adapted to register a longer list of elements — including possibly sounds, smells, time of day and chronology — when an experience occurred in relation to others.
Single-cell recordings cannot capture the entire array of circuitry involved in memory, which may be widely distributed beyond the hippocampus area, experts said. And as time passes, memories are consolidated, submerged, perhaps retooled and often entirely reshaped when retrieved later.
Though it did not address this longer-term process, the new study suggests that at least some of the neurons that fire when a distant memory comes to mind are those that were most active back when it happened, however long ago that was.
“The exciting thing about this,” said Dr. Kahana, the University of Pennsylvania professor, “is that it gives us direct biological evidence of what before was almost entirely theoretical.”
List of medications with potential safety problems
06 sept 2008--Drugs under investigation by the Food and Drug Administration, what they are used for and the potential problem: _R-Gene 10, a growth hormone, pediatric overdose due to labeling/packaging confusion. _Suprane, an anesthetic, cardiac arrest. _Cymbalta, for depression and other conditions, urinary retention. _Intelence, an HIV medication, bleeding into joints. _Carac and Kuric, creams for skin conditions and fungal infections, name confusion. _Heparin, a blood-thinner, serious allergic reactions. _Extraneal, used in kidney dialysis, low blood sugars. _Humulin R (U-500), insulin for diabetes, dosing confusion. _Stromectol and Warfarin, an anti-parasite drug and a blood thinner, drug interaction. _Tykerb, for advanced breast cancer, liver damage. _Revlimid, for multiple myeloma, severe skin blistering and bleeding. _Tysabri, for multiple sclerosis, skin melanomas. _Nitrostat, for angina, overdose due to labeling confusion. _Sandostatin LAR, for abnormal bone growth, bowel obstruction. _Oxycontin, a pain killer, drug misuse, abuse and overdose. _Definity, used in cardiac imaging, cardiopulmonary reactions. _Dilantin injection, for epileptic seizures, serious skin reaction. _Seroquel, for bipolar disorder, overdose due to sample pack labeling confusion. _Tyzeka, for chronic hepatitis B, nerve damage. _Tumor Necrosis Factor (TNF) Blockers, for juvenile arthritis, cancers in children and young adults.
06 sept 2008--Drugs under investigation by the Food and Drug Administration, what they are used for and the potential problem: _R-Gene 10, a growth hormone, pediatric overdose due to labeling/packaging confusion. _Suprane, an anesthetic, cardiac arrest. _Cymbalta, for depression and other conditions, urinary retention. _Intelence, an HIV medication, bleeding into joints. _Carac and Kuric, creams for skin conditions and fungal infections, name confusion. _Heparin, a blood-thinner, serious allergic reactions. _Extraneal, used in kidney dialysis, low blood sugars. _Humulin R (U-500), insulin for diabetes, dosing confusion. _Stromectol and Warfarin, an anti-parasite drug and a blood thinner, drug interaction. _Tykerb, for advanced breast cancer, liver damage. _Revlimid, for multiple myeloma, severe skin blistering and bleeding. _Tysabri, for multiple sclerosis, skin melanomas. _Nitrostat, for angina, overdose due to labeling confusion. _Sandostatin LAR, for abnormal bone growth, bowel obstruction. _Oxycontin, a pain killer, drug misuse, abuse and overdose. _Definity, used in cardiac imaging, cardiopulmonary reactions. _Dilantin injection, for epileptic seizures, serious skin reaction. _Seroquel, for bipolar disorder, overdose due to sample pack labeling confusion. _Tyzeka, for chronic hepatitis B, nerve damage. _Tumor Necrosis Factor (TNF) Blockers, for juvenile arthritis, cancers in children and young adults.
How STDs increase the risk of becoming infected with HIV
06 sept 2008--Individuals who have a sexually transmitted disease (e.g., genital herpes, gonorrhea, syphilis, and chlamydia) and women with yeast and bacterial vaginal infections have an increased risk of becoming infected with HIV if exposed to the virus through sexual contact. Although several explanations have been proposed, exactly how and why STDs have this effect has not been clear. Now, Teunis B.H. Geijtenbeek and colleagues, at VU University Medical Center, The Netherlands, have described a way in which STDs can increase acquisition of HIV-1 infection in an ex vivo human skin explant model that they hope might be amenable to therapeutic modulation to prevent HIV transmission.
In the ex vivo human skin explant model, although immature immune cells known as Langerhans cells (LCs) captured HIV, they did not efficiently transmit the virus to T cells, something that is essential for the initiation of full disease. By contrast, efficient virus transmission was observed if LCs were activated by inflammatory stimuli. As the infectious agents that cause the STDs thrush and gonorrhea triggered the same inflammatory stimuli in vaginal and skin explants, the authors suggest that in the presence of an STD-causing infectious agent, LCs might become activated, thereby increasing an individual's risk of becoming infected with HIV. Further, these data suggest that antiinflammatory therapies might provide a way to prevent HIV transmission.
###
TITLE: TNF-alpha and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo
AUTHOR CONTACT: Teunis B.H. Geijtenbeek VU University Medical Center, Amsterdam, The Netherlands. Phone: (31) 20-4448080; Fax: (31) 20-4448081; E-mail: T.Geijtenbeek@vumc.nl.
06 sept 2008--Individuals who have a sexually transmitted disease (e.g., genital herpes, gonorrhea, syphilis, and chlamydia) and women with yeast and bacterial vaginal infections have an increased risk of becoming infected with HIV if exposed to the virus through sexual contact. Although several explanations have been proposed, exactly how and why STDs have this effect has not been clear. Now, Teunis B.H. Geijtenbeek and colleagues, at VU University Medical Center, The Netherlands, have described a way in which STDs can increase acquisition of HIV-1 infection in an ex vivo human skin explant model that they hope might be amenable to therapeutic modulation to prevent HIV transmission.
In the ex vivo human skin explant model, although immature immune cells known as Langerhans cells (LCs) captured HIV, they did not efficiently transmit the virus to T cells, something that is essential for the initiation of full disease. By contrast, efficient virus transmission was observed if LCs were activated by inflammatory stimuli. As the infectious agents that cause the STDs thrush and gonorrhea triggered the same inflammatory stimuli in vaginal and skin explants, the authors suggest that in the presence of an STD-causing infectious agent, LCs might become activated, thereby increasing an individual's risk of becoming infected with HIV. Further, these data suggest that antiinflammatory therapies might provide a way to prevent HIV transmission.
###
TITLE: TNF-alpha and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo
AUTHOR CONTACT: Teunis B.H. Geijtenbeek VU University Medical Center, Amsterdam, The Netherlands. Phone: (31) 20-4448080; Fax: (31) 20-4448081; E-mail: T.Geijtenbeek@vumc.nl.
Carotid Artery Surgery in Dead Heat with Angioplasty and Stenting
By John Gever
PARIS, 06 sept 2008-- Medium-term efficacy is about the same for carotid endarterectomy versus angioplasty and stenting, said researchers here and in Germany. In two randomized studies involving nearly 1,500 patients and two to four years of follow-up, rates of ipsilateral stroke and death were nearly equal when events within the first month were excluded. The four-year risk of ipsilateral stroke after the first 30 days was 1.26% (95% CI 0% to 3%) for stented patients compared with 1.97% (95% CI 0% to 4%) for patients undergoing endarterectomy, reported Jean-Louis Mas, M.D., of the Hôpitaux Sainte-Anne, and colleagues online in Lancet Neurology. They were reporting final results from the EVA-3S (Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis) trial, in which 262 patients with recent-onset symptoms were randomized to one of the two procedures.
Reported simultaneously was a study by Peter Ringleb, M.D., of the University of Heidelberg, Germany, and his colleagues in the international SPACE (Stent-Protected Angioplasty versus Carotid Endarterectomy) collaboration.
In their 1,214-patient randomized trial, 12 stented patients and 10 receiving surgery suffered ipsilateral strokes after day 30, with two years of follow-up. They calculated a hazard ratio for non-periprocedural ipsilateral stroke of 1.17 (95% CI 0.51 to 2.70) on an intent-to-treat basis.
Both groups had previously reported 30-day results in which rates of death and stroke were significantly higher for angioplasty and stenting than for endarterectomy. In their current report, Dr. Mas and colleagues acknowledged that "the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy."
But for patients who avoid the short-term hazards, they added, "carotid stenting is as effective as carotid endarterectomy for medium-term prevention of ipsilateral stroke, at least for the first 4 years after the perioperative period."
Dr. Ringleb and colleagues found that even when the higher periprocedural rates of death and stroke were included in the results, there was no significant difference in outcomes for the two procedures.
They calculated intent-to-treat hazard ratios for periprocedural events plus late ipsilateral strokes of 1.10 (95% CI 0.75 to 1.61) for stenting relative to endarterectomy.
Cumulative two-year risks on the same basis were 9.5% for stenting versus 8.8% for endarterectomy.
Despite the similarities in rates of late strokes, the SPACE investigators found restenosis in 10.7% of stented patients compared with 4.6% of the endarterectomy group (P=0.0009).
But only two of the stented patients with restenosis showed neurological symptoms, the researchers said.
They also argued that the ultrasound technology they used to measure the vascular lumen may overestimate stenosis in stented vessels.
In an accompanying editorial, A. Ross Naylor, M.D., M.B.Ch.B., of the University of Leicester, England, noted that most previous studies have found in favor of endarterectomy over angioplasty and stenting.
The SPACE and EVA-3S results are unlikely to overturn that judgment, he said, but they do offer some intriguing new insights.
"The most important finding ... is recognition that the average annual risk of ipsilateral stroke is 1% or less, irrespective of whether the patient was treated by carotid endarterectomy or [stenting]," Dr. Naylor wrote.
He also found it notable that the SPACE study found equivalent late stroke rates despite the higher apparent incidence of restenosis in the stented patients. Dr. Naylor said the finding suggested restenosis "is a relatively benign pathology."
A third major result from the studies, according to Dr. Naylor, was that outcomes for angioplasty and stenting seemed to be strongly influenced by age, with older patients faring less well.
He said the next step should be a pooled analysis of data from all the large randomized trials, including two still underway. The goal would be to identify subgroups who benefit the most, and least, from the two procedures, as well as other aspects of treatment that affect outcomes.
Primary source: Lancet NeurologySource reference:Mas J-L, et al "Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial" Lancet Neurology 2008; DOI: 10.1016/S1474-4422(08)70195-9.
Additional source: Lancet NeurologySource reference: Eckstein H-H, et al "Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial" Lancet Neurology 2008; DOI: 10.1016/S1474-4422(08)70196-0. Additional source: Lancet NeurologySource reference: Naylor A "Stenting versus endarterectomy: the debate continues" Lancet Neurology 2008; DOI: 10.1016/S1474-4422(08)70197-2.
By John Gever
PARIS, 06 sept 2008-- Medium-term efficacy is about the same for carotid endarterectomy versus angioplasty and stenting, said researchers here and in Germany. In two randomized studies involving nearly 1,500 patients and two to four years of follow-up, rates of ipsilateral stroke and death were nearly equal when events within the first month were excluded. The four-year risk of ipsilateral stroke after the first 30 days was 1.26% (95% CI 0% to 3%) for stented patients compared with 1.97% (95% CI 0% to 4%) for patients undergoing endarterectomy, reported Jean-Louis Mas, M.D., of the Hôpitaux Sainte-Anne, and colleagues online in Lancet Neurology. They were reporting final results from the EVA-3S (Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis) trial, in which 262 patients with recent-onset symptoms were randomized to one of the two procedures.
Reported simultaneously was a study by Peter Ringleb, M.D., of the University of Heidelberg, Germany, and his colleagues in the international SPACE (Stent-Protected Angioplasty versus Carotid Endarterectomy) collaboration.
In their 1,214-patient randomized trial, 12 stented patients and 10 receiving surgery suffered ipsilateral strokes after day 30, with two years of follow-up. They calculated a hazard ratio for non-periprocedural ipsilateral stroke of 1.17 (95% CI 0.51 to 2.70) on an intent-to-treat basis.
Both groups had previously reported 30-day results in which rates of death and stroke were significantly higher for angioplasty and stenting than for endarterectomy. In their current report, Dr. Mas and colleagues acknowledged that "the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy."
But for patients who avoid the short-term hazards, they added, "carotid stenting is as effective as carotid endarterectomy for medium-term prevention of ipsilateral stroke, at least for the first 4 years after the perioperative period."
Dr. Ringleb and colleagues found that even when the higher periprocedural rates of death and stroke were included in the results, there was no significant difference in outcomes for the two procedures.
They calculated intent-to-treat hazard ratios for periprocedural events plus late ipsilateral strokes of 1.10 (95% CI 0.75 to 1.61) for stenting relative to endarterectomy.
Cumulative two-year risks on the same basis were 9.5% for stenting versus 8.8% for endarterectomy.
Despite the similarities in rates of late strokes, the SPACE investigators found restenosis in 10.7% of stented patients compared with 4.6% of the endarterectomy group (P=0.0009).
But only two of the stented patients with restenosis showed neurological symptoms, the researchers said.
They also argued that the ultrasound technology they used to measure the vascular lumen may overestimate stenosis in stented vessels.
In an accompanying editorial, A. Ross Naylor, M.D., M.B.Ch.B., of the University of Leicester, England, noted that most previous studies have found in favor of endarterectomy over angioplasty and stenting.
The SPACE and EVA-3S results are unlikely to overturn that judgment, he said, but they do offer some intriguing new insights.
"The most important finding ... is recognition that the average annual risk of ipsilateral stroke is 1% or less, irrespective of whether the patient was treated by carotid endarterectomy or [stenting]," Dr. Naylor wrote.
He also found it notable that the SPACE study found equivalent late stroke rates despite the higher apparent incidence of restenosis in the stented patients. Dr. Naylor said the finding suggested restenosis "is a relatively benign pathology."
A third major result from the studies, according to Dr. Naylor, was that outcomes for angioplasty and stenting seemed to be strongly influenced by age, with older patients faring less well.
He said the next step should be a pooled analysis of data from all the large randomized trials, including two still underway. The goal would be to identify subgroups who benefit the most, and least, from the two procedures, as well as other aspects of treatment that affect outcomes.
Primary source: Lancet NeurologySource reference:Mas J-L, et al "Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial" Lancet Neurology 2008; DOI: 10.1016/S1474-4422(08)70195-9.
Additional source: Lancet NeurologySource reference: Eckstein H-H, et al "Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial" Lancet Neurology 2008; DOI: 10.1016/S1474-4422(08)70196-0. Additional source: Lancet NeurologySource reference: Naylor A "Stenting versus endarterectomy: the debate continues" Lancet Neurology 2008; DOI: 10.1016/S1474-4422(08)70197-2.
African-Americans have unique lung cancer risks from chronic obstructive pulmonary disease
PHILADELPHIA, 06 sept 2008 – Scientists at the M.D. Anderson Cancer Center have developed a risk prediction assessment for lung cancer specifically for African Americans that suggests a greater risk from chronic obstructive pulmonary disease (COPD), according to a report published in the September issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.
Etzel and colleagues analyzed data from 491 African Americans with lung cancer and 497 African Americans without lung cancer to identify risk factors for the disease. They then compared these risk factors with a previously established risk prediction model for whites.
What was unique to African Americans was the risk associated with chronic obstructive pulmonary disease. African American men with a prior history of chronic obstructive pulmonary disease had a more than sixfold increased risk of lung cancer, similar to that seen with smoking. This is approximately two-fold higher than the risk typically seen from chronic obstructive pulmonary disease among whites.
"The one size fits all risk prediction clearly does not work," said Carol Etzel, Ph.D., assistant professor of epidemiology at the University of Texas M.D. Anderson Cancer Center.
As with whites, smoking was a significant risk factor for lung cancer. Current smokers had a more than sixfold increased risk of lung cancer, and former smokers had a more than threefold increased risk. This decreased risk was confined to those who had quit smoking more than ten years prior to diagnosis; these patients had a 58 percent decreased risk compared with patients who had quit within the previous ten years.
Researchers also found that hay fever, previously shown to be protective among whites, was also protective among African Americans. Specifically, African Americans with hay fever were 44 percent less likely to develop lung cancer, a rate that had been previously seen among whites.
African American males have a higher risk of lung cancer incidence at 110.6 per 100,000 compared with 81 per 100,000 among white males. Mortality is also higher among African American men at 95.8 per 100,000 compared with 72.6 among whites. Lung cancer incidence and mortality rates among women are comparable.
Etzel said the risk prediction model detailed in Cancer Prevention Research is part of an ongoing project to establish risk models among different ethnic groups; a model for Hispanics is currently under development.
"What we hope is that a doctor can use these models to encourage their patients to take steps to prevent lung cancer. Even if they are never smokers, they can be at risk," said Etzel.
PHILADELPHIA, 06 sept 2008 – Scientists at the M.D. Anderson Cancer Center have developed a risk prediction assessment for lung cancer specifically for African Americans that suggests a greater risk from chronic obstructive pulmonary disease (COPD), according to a report published in the September issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.
Etzel and colleagues analyzed data from 491 African Americans with lung cancer and 497 African Americans without lung cancer to identify risk factors for the disease. They then compared these risk factors with a previously established risk prediction model for whites.
What was unique to African Americans was the risk associated with chronic obstructive pulmonary disease. African American men with a prior history of chronic obstructive pulmonary disease had a more than sixfold increased risk of lung cancer, similar to that seen with smoking. This is approximately two-fold higher than the risk typically seen from chronic obstructive pulmonary disease among whites.
"The one size fits all risk prediction clearly does not work," said Carol Etzel, Ph.D., assistant professor of epidemiology at the University of Texas M.D. Anderson Cancer Center.
As with whites, smoking was a significant risk factor for lung cancer. Current smokers had a more than sixfold increased risk of lung cancer, and former smokers had a more than threefold increased risk. This decreased risk was confined to those who had quit smoking more than ten years prior to diagnosis; these patients had a 58 percent decreased risk compared with patients who had quit within the previous ten years.
Researchers also found that hay fever, previously shown to be protective among whites, was also protective among African Americans. Specifically, African Americans with hay fever were 44 percent less likely to develop lung cancer, a rate that had been previously seen among whites.
African American males have a higher risk of lung cancer incidence at 110.6 per 100,000 compared with 81 per 100,000 among white males. Mortality is also higher among African American men at 95.8 per 100,000 compared with 72.6 among whites. Lung cancer incidence and mortality rates among women are comparable.
Etzel said the risk prediction model detailed in Cancer Prevention Research is part of an ongoing project to establish risk models among different ethnic groups; a model for Hispanics is currently under development.
"What we hope is that a doctor can use these models to encourage their patients to take steps to prevent lung cancer. Even if they are never smokers, they can be at risk," said Etzel.
1 step back ... 2 steps forward
Early phase breast cancer study at GUMC suggests new approach can re-sensitize tumors
Washington, DC, 06 sept 2008—Women with hormone-receptor positive, metastatic breast cancer may take medications for years to help keep their cancer at bay, but when the tumor becomes resistant to anti-hormonal drugs, treatment with chemotherapy becomes the only option. But a study presented today at the 2008 ASCO Breast Cancer Symposiummay change this approach. Early data suggests a new treatment approach can "re-sensitize" the tumor, allowing anti-hormonal drugs to do their job once again.
The strategy being investigated involves breast cancers that are fueled by estrogen—these are called estrogen-receptor or progesterone-receptor positive cancers (ER or PR positive). Women who have ER or PR positive metastatic breast cancer often take anti-hormonal medicines, such as aromatase inhibitors, to keep the cancer from progressing. Aromatase inhibitors lower the amount of estrogen in the body. Over time, however, the cancer becomes resistant to this approach and begins to grow.
"At first, the tumor's growth is halted because the aromatase inhibitor is depriving the cancer of the estrogen it needs to grow," says Claudine Isaacs, M.D., clinical director of breast cancer program at Georgetown University Medical Center's Lombardi Comprehensive Cancer Center. "Eventually, though, the cancer will figure out another way to thrive in the absence of the estrogen."
Isaacs and her colleagues, including lead author Deepa Subramaniam, M.D. of Lombardi, are conducting a clinical trial to see if a new approach can destroy the machinery the tumor creates in order to grow without the estrogen. The drug being studied is called sorafenib.
The results of the phase II study involving 27 patients were presented today at the ASCO 2008 Breast Cancer Symposium. It included post-menopausal women with metastatic breast cancer whose cancer had recurred or progressed while taking the aromatase inhibitor anastrozole. The preliminary analysis shows a clinical benefit response in 26 percent of the patients taking both sorafenib and anastrozole.
"Given what we know about the ineffectiveness of sorafenib alone in metastatic breast cancer, we believe the benefit that we're seeing may be attributable to the restoration of sensitivity to aromatase inhibitors," Isaacs concludes. "To manage breast cancer long term, it's apparent that we may need to continually switch drugs to keep up with how a cancer evolves and evades each approach. In a sense, for each step back, we hope to take two steps forward."
###
This study was funded by the Avon Patient for Progress Award. Isaacs is part of a speaker's bureau for Pfizer the maker of Exemestane, an aromatase inhibitor.
Early phase breast cancer study at GUMC suggests new approach can re-sensitize tumors
Washington, DC, 06 sept 2008—Women with hormone-receptor positive, metastatic breast cancer may take medications for years to help keep their cancer at bay, but when the tumor becomes resistant to anti-hormonal drugs, treatment with chemotherapy becomes the only option. But a study presented today at the 2008 ASCO Breast Cancer Symposiummay change this approach. Early data suggests a new treatment approach can "re-sensitize" the tumor, allowing anti-hormonal drugs to do their job once again.
The strategy being investigated involves breast cancers that are fueled by estrogen—these are called estrogen-receptor or progesterone-receptor positive cancers (ER or PR positive). Women who have ER or PR positive metastatic breast cancer often take anti-hormonal medicines, such as aromatase inhibitors, to keep the cancer from progressing. Aromatase inhibitors lower the amount of estrogen in the body. Over time, however, the cancer becomes resistant to this approach and begins to grow.
"At first, the tumor's growth is halted because the aromatase inhibitor is depriving the cancer of the estrogen it needs to grow," says Claudine Isaacs, M.D., clinical director of breast cancer program at Georgetown University Medical Center's Lombardi Comprehensive Cancer Center. "Eventually, though, the cancer will figure out another way to thrive in the absence of the estrogen."
Isaacs and her colleagues, including lead author Deepa Subramaniam, M.D. of Lombardi, are conducting a clinical trial to see if a new approach can destroy the machinery the tumor creates in order to grow without the estrogen. The drug being studied is called sorafenib.
The results of the phase II study involving 27 patients were presented today at the ASCO 2008 Breast Cancer Symposium. It included post-menopausal women with metastatic breast cancer whose cancer had recurred or progressed while taking the aromatase inhibitor anastrozole. The preliminary analysis shows a clinical benefit response in 26 percent of the patients taking both sorafenib and anastrozole.
"Given what we know about the ineffectiveness of sorafenib alone in metastatic breast cancer, we believe the benefit that we're seeing may be attributable to the restoration of sensitivity to aromatase inhibitors," Isaacs concludes. "To manage breast cancer long term, it's apparent that we may need to continually switch drugs to keep up with how a cancer evolves and evades each approach. In a sense, for each step back, we hope to take two steps forward."
###
This study was funded by the Avon Patient for Progress Award. Isaacs is part of a speaker's bureau for Pfizer the maker of Exemestane, an aromatase inhibitor.
Friday, September 05, 2008
Tobacco caused 2.4 million U.S. cancers: report
05 sept 2008--Tobacco use caused 2.4 million cases of cancer in the United States from 1999 to 2004, the Centers for Disease Control and Prevention reported on Thursday.
As might be expected, lung and bronchial cancer accounted for nearly half the cases but cancers of the larynx, mouth and pharynx, esophagus, stomach, pancreas, kidney, bladder, cervix, as well as acute myelogenous leukemia are also caused by tobacco, the CDC found.
"The data in this report provides additional, strong evidence of the serious harm related to tobacco," said Sherri Stewart of the CDC's Division of Cancer Prevention and Control, who led the study.
Stewart's team looked at cancer surveys and registries covering 92 percent of the U.S. population.
Kentucky had the highest rates of lung cancer among men and women, while Western states with low rates of smoking also had low rates of cancer.
Tobacco-related cancers were more common among blacks, non-Hispanic whites and men, reflecting the groups that use tobacco more, the CDC found.
"Tobacco use is the leading preventable cause of disease and premature death in the United States and the most prominent cause of cancer," said the CDC's Dr. Matthew McKenna.
"The tobacco-use epidemic causes a third of the cancers in America."
Tobacco use kills 438,000 people prematurely every year, including 38,000 people who breathe only secondhand smoke, the CDC said.
"Tobacco use causes more deaths each year than alcohol use, car crashes, suicide, acquired immunodeficiency syndrome (AIDS), homicide, and illegal drug use combined," the report reads.
"In addition, smoking accounts for $167 billion annually in health care expenditures and productivity losses."
As might be expected, lung and bronchial cancer accounted for nearly half the cases but cancers of the larynx, mouth and pharynx, esophagus, stomach, pancreas, kidney, bladder, cervix, as well as acute myelogenous leukemia are also caused by tobacco, the CDC found.
"The data in this report provides additional, strong evidence of the serious harm related to tobacco," said Sherri Stewart of the CDC's Division of Cancer Prevention and Control, who led the study.
Stewart's team looked at cancer surveys and registries covering 92 percent of the U.S. population.
Kentucky had the highest rates of lung cancer among men and women, while Western states with low rates of smoking also had low rates of cancer.
Tobacco-related cancers were more common among blacks, non-Hispanic whites and men, reflecting the groups that use tobacco more, the CDC found.
"Tobacco use is the leading preventable cause of disease and premature death in the United States and the most prominent cause of cancer," said the CDC's Dr. Matthew McKenna.
"The tobacco-use epidemic causes a third of the cancers in America."
Tobacco use kills 438,000 people prematurely every year, including 38,000 people who breathe only secondhand smoke, the CDC said.
"Tobacco use causes more deaths each year than alcohol use, car crashes, suicide, acquired immunodeficiency syndrome (AIDS), homicide, and illegal drug use combined," the report reads.
"In addition, smoking accounts for $167 billion annually in health care expenditures and productivity losses."
FDA orders stronger warnings for 4 arthritis drugs
WASHINGTON , 05 sept 2008-- The Food and Drug Administration ordered stronger warnings Thursday on four medications widely used to treat rheumatoid arthritis and other serious illnesses, saying they can raise the risk of possibly fatal fungal infections.
The drugs -- Enbrel, Remicade, Humira and Cimzia -- work by suppressing the immune system to keep it from attacking the body. For patients with rheumatoid arthritis, the treatment provides relief from swollen and painful joints, but it's ''a double-edged sword,'' said the FDA's Dr. Jeffrey Siegel. That's because the drugs also lower the body's defenses to various kinds of infections.
Siegel, who heads the office that oversees arthritis drugs, said the FDA became concerned after discovering that doctors seemed to be overlooking a particular kind of fungal infection called histoplasmosis. Of 240 cases reported to the FDA in which patients taking one of the four drugs developed this infection, a total of 45 died -- about 20 percent.
The infection, which mimics the flu, is prevalent in much of the middle part of the country. It can have particularly grave consequences if it isn't caught early and spreads beyond the respiratory system to other organs of the body.
Siegel said the investigation began with a single case of a woman taking one of the drugs who died of histoplasmosis. Delving into the case, doctors at the FDA found that the woman had been sick with the fungal infection for a long time. ''This case led us to be concerned that there may be other situations in which physicians may not recognize histoplasmosis,'' said Siegel.
FDA officials searched the agency's database and found the 240 cases of patients taking the medications who had also developed the fungal infection. Of those, at least 21 appeared to involve a late diagnosis, and 12 of them -- more than half -- ultimately died.
Siegel said the FDA's order Thursday means that the risk of histoplasmosis will be flagged in a ''black box,'' the strongest warning information in a drug's prescribing literature. The four medications already have black box warnings about the risk of infections, but the language varies from drug to drug.
Patients should call their doctors if they develop persistent fever, cough, shortness of breath or fatigue, which can be signs of the fungal infection.
And the FDA is also urging doctors to consider aggressive use of antifungal drugs in patients who develop such symptoms, even if the infection has not been confirmed by a laboratory test. Siegel said such a decision should not be taken lightly, since antifungal drugs can also have dangerous side effects. Doctors should consider stopping treatment with the immune-suppressing drugs if patients develop infections.
The four drugs belong to a class known as TNF-alpha blockers, and are considered a mainstay for treating rheumatoid arthritis, a disabling disease in which the immune system attacks the joints. They are also used to treat Crohn's disease, juvenile arthritis, certain types of psoriasis, and other immune system disorders. All are taken by injection.
Separately, the FDA is investigating a possible link between the four medications and cancer in young patients. The agency said earlier this year it has received 30 reports of cancers, mainly lymphomas, in patients who began taking the medications when they were 18 or younger. That investigation is expected to take the rest of the year.
Three of the drugs, Enbrel, Humira and Remicade, are considered blockbusters, with sales of over $1 billion annually for each. Cimzia is newer and less widely used.
Humira is sold by North Chicago, Ill.-based Abbott Laboratories Inc; Cimzia by Belgium-based UCB; Enbrel by Thousand Oaks, Calif.-based Amgen Inc. and Madison, N.J.-based Wyeth; and Remicade by Horsham, Pa.-based Centocor, a unit of Johnson & Johnson, and Kenilworth, N.J.-based Schering-Plough Inc.
WASHINGTON , 05 sept 2008-- The Food and Drug Administration ordered stronger warnings Thursday on four medications widely used to treat rheumatoid arthritis and other serious illnesses, saying they can raise the risk of possibly fatal fungal infections.
The drugs -- Enbrel, Remicade, Humira and Cimzia -- work by suppressing the immune system to keep it from attacking the body. For patients with rheumatoid arthritis, the treatment provides relief from swollen and painful joints, but it's ''a double-edged sword,'' said the FDA's Dr. Jeffrey Siegel. That's because the drugs also lower the body's defenses to various kinds of infections.
Siegel, who heads the office that oversees arthritis drugs, said the FDA became concerned after discovering that doctors seemed to be overlooking a particular kind of fungal infection called histoplasmosis. Of 240 cases reported to the FDA in which patients taking one of the four drugs developed this infection, a total of 45 died -- about 20 percent.
The infection, which mimics the flu, is prevalent in much of the middle part of the country. It can have particularly grave consequences if it isn't caught early and spreads beyond the respiratory system to other organs of the body.
Siegel said the investigation began with a single case of a woman taking one of the drugs who died of histoplasmosis. Delving into the case, doctors at the FDA found that the woman had been sick with the fungal infection for a long time. ''This case led us to be concerned that there may be other situations in which physicians may not recognize histoplasmosis,'' said Siegel.
FDA officials searched the agency's database and found the 240 cases of patients taking the medications who had also developed the fungal infection. Of those, at least 21 appeared to involve a late diagnosis, and 12 of them -- more than half -- ultimately died.
Siegel said the FDA's order Thursday means that the risk of histoplasmosis will be flagged in a ''black box,'' the strongest warning information in a drug's prescribing literature. The four medications already have black box warnings about the risk of infections, but the language varies from drug to drug.
Patients should call their doctors if they develop persistent fever, cough, shortness of breath or fatigue, which can be signs of the fungal infection.
And the FDA is also urging doctors to consider aggressive use of antifungal drugs in patients who develop such symptoms, even if the infection has not been confirmed by a laboratory test. Siegel said such a decision should not be taken lightly, since antifungal drugs can also have dangerous side effects. Doctors should consider stopping treatment with the immune-suppressing drugs if patients develop infections.
The four drugs belong to a class known as TNF-alpha blockers, and are considered a mainstay for treating rheumatoid arthritis, a disabling disease in which the immune system attacks the joints. They are also used to treat Crohn's disease, juvenile arthritis, certain types of psoriasis, and other immune system disorders. All are taken by injection.
Separately, the FDA is investigating a possible link between the four medications and cancer in young patients. The agency said earlier this year it has received 30 reports of cancers, mainly lymphomas, in patients who began taking the medications when they were 18 or younger. That investigation is expected to take the rest of the year.
Three of the drugs, Enbrel, Humira and Remicade, are considered blockbusters, with sales of over $1 billion annually for each. Cimzia is newer and less widely used.
Humira is sold by North Chicago, Ill.-based Abbott Laboratories Inc; Cimzia by Belgium-based UCB; Enbrel by Thousand Oaks, Calif.-based Amgen Inc. and Madison, N.J.-based Wyeth; and Remicade by Horsham, Pa.-based Centocor, a unit of Johnson & Johnson, and Kenilworth, N.J.-based Schering-Plough Inc.
New Screening Catches More Breast Cancers
By Amanda Gardner
05 sept 2008-- While tremendous progress in screening and treatment for breast cancer has been made in recent years, some 184,000 new cases of breast cancer will be diagnosed in the United States in 2008, and about 41,000 women will die of the disease.
Researchers are now focusing their efforts on reducing these numbers even further.
Four studies being presented this week at the American Society of Clinical Oncology's 2008 Breast Cancer Symposium in Washington, D.C., highlight both areas of progress and areas that need extra emphasis.
A screening technique known as molecular breast imaging (MBI) detected three times as many breast cancers in women who have dense breasts and who are at a higher risk of developing the disease. These findings suggest that MBI could one day be added to conventional mammography.
Using an injected radiotracer (provided, for this study, by Bristol-Myers Squibb), MBI is able to detect differences in the behavior of cancer tissue as compared to normal tissue.
In this study, MBI detected 10 of 13 cancers among 375 patients completing a 15-month follow-up period. Mammography, by contrast, detected three of 13 cancers.
"If we had had a combination of both techniques, we would have detected 11 of 13 cancers," said study author Carrie B. Hruska, a research fellow in the department of radiology at the Mayo Clinic in Rochester, Minn. "MBI detected more cancers than screening mammography but didn't produce more false positive results."
Hruska spoke at a Wednesday teleconference with authors of the three other studies.
Also, the number of biopsies that actually resulted in cancer was much higher with MBI (28 percent) than with mammography (18 percent).
"Based on the results, MBI has shown great promise as a valuable adjunct to screening mammography in women with dense breasts and who are at an increased risk of developing cancer," Hruska said.
But while relatively inexpensive and easy to use, MBI is not yet widely available.
"This is an area that is very important, and where we really need to do further work," said Dr. Eric Winer, moderator of the teleconference and director of the breast oncology center at Dana-Farber Cancer Institute in Boston.
A second study, conducted by researchers at Johns Hopkins University, debunks the long-held notion that women in rural areas are more likely to chose mastectomy over lumpectomy because of difficulty traveling to radiation facilities.
Radiation is considered standard-of-care for women after they have received a breast-conserving lumpectomy, although not for women who undergo a mastectomy.
There were no notable differences between radiation rates following lumpectomy for women in rural areas as compared with women in urban areas, although the study did confirm that more women in rural areas (59.9 percent) opted for mastectomy, versus 44.9 percent of women in urban areas.
"The disparity . . . is not necessarily due to the availability of radiation therapy but to other factors," said study author Dr. Lisa K. Jacobs, an assistant professor of surgery at Johns Hopkins University in Baltimore.
"This would seem to suggest that if a woman in a rural area chooses to have a lumpectomy, she will most likely not fall through the cracks in terms of getting radiation, which is somewhat reassuring," Winer said. "But it would be interesting to look at this further."
In a third study, researchers at M.D. Anderson Cancer Center in Houston found that older black women undergoing lumpectomy for early-stage invasive breast cancer were less likely to receive recommended post-surgery radiation therapy than their white counterparts.
Only 65 percent of black women received radiation, compared with 74 percent of white women. "The difference is concerning, given that radiation after lumpectomy is generally considered standard therapy," said study author Dr. Grace Smith, a postdoctoral fellow in the department of radiation oncology at Anderson.
Disparities also existed in the younger range (women aged 65 to 70) of this older group, who were less likely to have medical conditions precluding radiation therapy. Here, 71 percent of black women received potentially lifesaving radiation versus 81 percent of white women.
The largest disparities were evident in the East South Central region of the United States, the Pacific West and New England.
"What seems to be happening is that the use of conservative surgery and radiation opens the door for disparities to play a greater role in limiting access to care," Winer said. In this two-step process (surgery plus radiation), Winer added, "it is possible for women to fall through the cracks."
The final study addressed women with HER2-positive breast cancer, which traditionally has a worse prognosis than other forms of breast cancer.
Chemotherapy and treatment with Herceptin (trastuzumab) before surgery results in a "pathologic complete response," meaning no evidence of invasive disease in the breast or lymph nodes existed in many patients.
Patients who did not have this complete response were three times more likely to have a recurrence, the researchers from M.D. Anderson reported.
In about one-third of those not achieving a complete response, the cancer had converted from HER2-positive disease to HER2-negative disease, meaning it was no longer responsive and had possibly become resistant to HER2-specific therapies such as Herceptin.
The authors stressed the importance of reassessing tissue for HER2 status after preoperative treatment.
By Amanda Gardner
05 sept 2008-- While tremendous progress in screening and treatment for breast cancer has been made in recent years, some 184,000 new cases of breast cancer will be diagnosed in the United States in 2008, and about 41,000 women will die of the disease.
Researchers are now focusing their efforts on reducing these numbers even further.
Four studies being presented this week at the American Society of Clinical Oncology's 2008 Breast Cancer Symposium in Washington, D.C., highlight both areas of progress and areas that need extra emphasis.
A screening technique known as molecular breast imaging (MBI) detected three times as many breast cancers in women who have dense breasts and who are at a higher risk of developing the disease. These findings suggest that MBI could one day be added to conventional mammography.
Using an injected radiotracer (provided, for this study, by Bristol-Myers Squibb), MBI is able to detect differences in the behavior of cancer tissue as compared to normal tissue.
In this study, MBI detected 10 of 13 cancers among 375 patients completing a 15-month follow-up period. Mammography, by contrast, detected three of 13 cancers.
"If we had had a combination of both techniques, we would have detected 11 of 13 cancers," said study author Carrie B. Hruska, a research fellow in the department of radiology at the Mayo Clinic in Rochester, Minn. "MBI detected more cancers than screening mammography but didn't produce more false positive results."
Hruska spoke at a Wednesday teleconference with authors of the three other studies.
Also, the number of biopsies that actually resulted in cancer was much higher with MBI (28 percent) than with mammography (18 percent).
"Based on the results, MBI has shown great promise as a valuable adjunct to screening mammography in women with dense breasts and who are at an increased risk of developing cancer," Hruska said.
But while relatively inexpensive and easy to use, MBI is not yet widely available.
"This is an area that is very important, and where we really need to do further work," said Dr. Eric Winer, moderator of the teleconference and director of the breast oncology center at Dana-Farber Cancer Institute in Boston.
A second study, conducted by researchers at Johns Hopkins University, debunks the long-held notion that women in rural areas are more likely to chose mastectomy over lumpectomy because of difficulty traveling to radiation facilities.
Radiation is considered standard-of-care for women after they have received a breast-conserving lumpectomy, although not for women who undergo a mastectomy.
There were no notable differences between radiation rates following lumpectomy for women in rural areas as compared with women in urban areas, although the study did confirm that more women in rural areas (59.9 percent) opted for mastectomy, versus 44.9 percent of women in urban areas.
"The disparity . . . is not necessarily due to the availability of radiation therapy but to other factors," said study author Dr. Lisa K. Jacobs, an assistant professor of surgery at Johns Hopkins University in Baltimore.
"This would seem to suggest that if a woman in a rural area chooses to have a lumpectomy, she will most likely not fall through the cracks in terms of getting radiation, which is somewhat reassuring," Winer said. "But it would be interesting to look at this further."
In a third study, researchers at M.D. Anderson Cancer Center in Houston found that older black women undergoing lumpectomy for early-stage invasive breast cancer were less likely to receive recommended post-surgery radiation therapy than their white counterparts.
Only 65 percent of black women received radiation, compared with 74 percent of white women. "The difference is concerning, given that radiation after lumpectomy is generally considered standard therapy," said study author Dr. Grace Smith, a postdoctoral fellow in the department of radiation oncology at Anderson.
Disparities also existed in the younger range (women aged 65 to 70) of this older group, who were less likely to have medical conditions precluding radiation therapy. Here, 71 percent of black women received potentially lifesaving radiation versus 81 percent of white women.
The largest disparities were evident in the East South Central region of the United States, the Pacific West and New England.
"What seems to be happening is that the use of conservative surgery and radiation opens the door for disparities to play a greater role in limiting access to care," Winer said. In this two-step process (surgery plus radiation), Winer added, "it is possible for women to fall through the cracks."
The final study addressed women with HER2-positive breast cancer, which traditionally has a worse prognosis than other forms of breast cancer.
Chemotherapy and treatment with Herceptin (trastuzumab) before surgery results in a "pathologic complete response," meaning no evidence of invasive disease in the breast or lymph nodes existed in many patients.
Patients who did not have this complete response were three times more likely to have a recurrence, the researchers from M.D. Anderson reported.
In about one-third of those not achieving a complete response, the cancer had converted from HER2-positive disease to HER2-negative disease, meaning it was no longer responsive and had possibly become resistant to HER2-specific therapies such as Herceptin.
The authors stressed the importance of reassessing tissue for HER2 status after preoperative treatment.
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