By Nancy Walsh, Staff Writer, MedPage Today
Published: May 19, 2011
Rob Summers was 20 in the summer before his junior year at Oregon State University in the summer of 2006. A pitcher on the school's baseball team, he went out around midnight to get his gym bag out of his car when a hit-and-run driver jumped the curb, striking him and leaving him paralyzed with an injury to the spinal cord from C7-T1.
Today Summers can stand for several minutes and move his legs, feet, and toes. He has regained some bladder control and sexual functioning, as well as the ability to regulate his body temperature through mechanisms such as perspiration.
These gains are the result of unprecedented treatment -- begun in December 2009 -- using electrical stimulation of the spinal cord.
After 80 sessions of task-specific training, epidural stimulation from an implanted unit allowed Summers to stand, bearing all his weight, for up to 4.25 minutes, Susan Harkema, PhD, of the University of Louisville in Kentucky, V. Reggie Edgerton, PhD, of the University of California Los Angeles, and colleagues reported online in The Lancet.
Summers had previously undergone 26 months of locomotor training with assistance on a treadmill that had failed to produce any changes in electromyographic activity in the legs, the researchers explained.
"This unexpected recovery of supraspinally mediated movement suggests that activity-dependent mechanisms promoted plasticity of anxonal projections that presumably were spared by the injury," observed Grégoire Courtine, PhD, of the University of Zurich in Switzerland, and colleagues in a commentary accompanying the case report.
Animal studies had shown that the spinal cord is capable of generating motor commands without signals from the brain by means of neural networks known as central pattern generators.
In paralyzed humans, epidural stimulation has been shown to induce rhythmic movements of the legs while the patient lies supine.
Most [spinal cord injuries] involve a contusion or compressive injury of the cord that causes a great deal of damage, but leaves a certain number of nerve fibers that connect the brain with the spinal cord," Edward D. Hall, PhD, of the University of Kentucky and the Spinal Cord and Brain Injury Research Center in Lexington, observed in an email to ABC News and MedPage Today.
Harkema's team in Louisville had been doing research to see if spinal cord stimulation could activate neural circuits in the spine and, coupled with sensory input from the legs, permit standing and locomotion. Summers went to Louisville to see if they could help him.
In December of 2009, the team implanted a 16-electrode array over the young man's spinal segments L1-S1.
They also implanted a pulse generator connected to an electrode lead in the abdomen.
The researchers explained that, although Summers was paralyzed below the chest, he was classified as grade B on the American Spinal Injury Association's neurologic impairment scale since he had light touch sensation below the area of the spinal injury. But he had no voluntary control over the muscles of legs and trunk and no ability to contract the bladder.
The investigators tested various amplitudes ranging from 0.5 to 10 V and frequencies of 5 Hz to 40 Hz, in stimulation sessions ranging from 40 minutes to two hours.
Summers has reported tingling sensations at the site of the implanted electrode and in the muscles being activated, but did not experience pain during the stimulation sessions.
Initially, he was able to stand only with 65% body weight support, but over time he progressed to full weight bearing.
In addition to learning to stand unaided, Summers eventually progressed to the extent that he could stand up from a sitting position, which resulted in a marked increase in electromyographic activity.
He then learned task-specific sensory cues such as positioning of the legs, hips, and knees to accomplish step-like movements during 30 Hz to 40 Hz epidural stimulation.
But without the epidural stimulation, no electromyographic activity could be detected when his trainers assisted him in performing these stepping movements.
Hall cautioned that if this approach is shown to help in other patients, it may allow them to walk with the aid of a walker.
"While this will have value, it is important to note that it will not reproduce normal walking," Hall said.
If Summers isn't running around any baseball diamonds, he has a renewed sense of well being and self-esteem. Now 25, he lives in Los Angeles. And last summer, he spent 10 days helping at a baseball camp in Florida.
"One possible explanation for this recovery is that residual supraspinal connections that existed but could not be detected clinically were reactivated or that new supraspinal connections to the spinal networks were formed," Edgarton's group noted in their paper.
"Challenges lie ahead," stated Courtine and colleagues in their commentary and the findings need to be replicated in a clinical trial with sufficient numbers of patients.
Nonetheless, they wrote, "The exceptional results bring new hope in a field that has remained unsatisfying -- with limited progress despite decades of research throughout the world."
Naomi Kleitman, PhD, of the National Institutes of Health in Bethesda, Md., also found Summers' story hopeful. Most people are unaware of the complex circuits in their spine that transmit commands to the body from the brain, she told MedPage Today and ABC News in an email.
"Spinal cord injuries break this vital connection but the sophisticated circuitry of the spinal cord remains, ready to coordinate stepping if it receives the right commands. Harnessing that potential has been the goal of decades of research to understand spinal cord function and to find effective ways to restore function after injury," Kleitman explained.
Thursday, May 19, 2011
Sunday, May 15, 2011
Scientists find "master switch" gene for obesity
LONDON (Reuters) – Scientists have found that a gene linked to diabetes and cholesterol is a "master switch" that controls other genes found in fat in the body, and say it should help in the search for treatments for obesity-related diseases.
In a study published in the journal Nature Genetics, the British researchers said that since fat plays an important role in peoples' susceptibility to metabolic diseases like obesity, heart disease and diabetes, the regulating gene could be target for drugs to treat such illnesses.
"This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes," said Tim Spector of King's College London, who led the study.
More than half a billion people, or one in 10 adults worldwide, are obese and the numbers have doubled since the 1980s as the obesity epidemic has spilled over from wealthy into poorer nations.
In the United States, obesity-related diseases already account for nearly 10 percent of medical spending -- an estimated $147 billion a year.
Type 2 diabetes, which is often linked to poor diet and lack of exercise, is also reaching epidemic levels worldwide as rates of obesity rise.
Scientists have already identified a gene called KLF14 as being linked to type 2 diabetes and cholesterol levels, but until now they did know what role it played.
Spector's team analyzed more than 20,000 genes in fat samples taken from under the skin of 800 British female twin volunteers. They found a link between the KLF14 gene and the levels of many other distant genes found in fat tissue, showing that KLF14 acts as a master switch to control these genes.
They then confirmed their findings in 600 fat samples from a separate group of people from Iceland.
In a report of their study, the researchers explained that other genes found to be controlled by KLF14 are linked to a range of metabolic traits, including body mass index, obesity, cholesterol, insulin and glucose levels.
"KLF14 seems to act as a master switch controlling processes that connect changes in the behavior of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions," said Mark McCarthy from Britain's Oxford University, who also worked on the study.
"We are working hard...to understand these processes and how we can use this information to improve treatment of these conditions."
(Reporting by Kate Kelland, editing by Mark Heinrich)
In a study published in the journal Nature Genetics, the British researchers said that since fat plays an important role in peoples' susceptibility to metabolic diseases like obesity, heart disease and diabetes, the regulating gene could be target for drugs to treat such illnesses.
"This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes," said Tim Spector of King's College London, who led the study.
More than half a billion people, or one in 10 adults worldwide, are obese and the numbers have doubled since the 1980s as the obesity epidemic has spilled over from wealthy into poorer nations.
In the United States, obesity-related diseases already account for nearly 10 percent of medical spending -- an estimated $147 billion a year.
Type 2 diabetes, which is often linked to poor diet and lack of exercise, is also reaching epidemic levels worldwide as rates of obesity rise.
Scientists have already identified a gene called KLF14 as being linked to type 2 diabetes and cholesterol levels, but until now they did know what role it played.
Spector's team analyzed more than 20,000 genes in fat samples taken from under the skin of 800 British female twin volunteers. They found a link between the KLF14 gene and the levels of many other distant genes found in fat tissue, showing that KLF14 acts as a master switch to control these genes.
They then confirmed their findings in 600 fat samples from a separate group of people from Iceland.
In a report of their study, the researchers explained that other genes found to be controlled by KLF14 are linked to a range of metabolic traits, including body mass index, obesity, cholesterol, insulin and glucose levels.
"KLF14 seems to act as a master switch controlling processes that connect changes in the behavior of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions," said Mark McCarthy from Britain's Oxford University, who also worked on the study.
"We are working hard...to understand these processes and how we can use this information to improve treatment of these conditions."
(Reporting by Kate Kelland, editing by Mark Heinrich)
Saturday, May 14, 2011
Heavy Coffee Intake Linked to Lower Breast Ca Risk
y Charles Bankhead, Staff Writer, MedPage Today
Published: May 13, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Activate MedPage Today's CME feature and receive free CME credit on medical stories like this oneAction Points
Point out that this study in Sweden found a statistically significant decrease in ER-negative breast cancer among postmenopausal women who had a high daily intake of coffee.
Note that the study is subject to residual confounding by unmeasured variables.
Women who drank at least five cups of coffee daily had a significantly lower risk of postmenopausal breast cancer, an analysis of two large cohort studies suggested.
Overall, the magnitude of the benefit ranged from 20% to more than 50% in unadjusted and adjusted analyses. Analysis of the results by estrogen receptor (ER) status showed that the favorable association pertained only to ER-negative cancers, according to an article published online in Breast Cancer Research.
"Coffee consumption was associated with a strong reduction in breast cancer risk for the ER-negative tumor subtype," Jingmei Li, PhD, of the Karolinska Institute in Stockholm, and co-authors wrote. "This effect was independent of hormone replacement therapy (HRT), smoking, highest education level attained, and average daily alcohol consumption."
"We speculate that coffee might contain compounds that differentially affect breast cancer of different ER subtypes," they added.
Coffee has a paradoxical relationship with breast cancer risk. The beverage's complex mix of caffeine and polyphenols suggests a potential to confer both carcinogenic and chemopreventive characteristics, the authors noted in the introduction to their study.
In general, previous studies have indicated that high coffee consumption might modestly reduce breast cancer risk. However, a meta-analysis of more than 500 reports about coffee's relationship to several types of cancer showed no association with breast cancer (Nutr Cancer 2010; 62: 271-283).
In an effort to add information to the knowledge base, Li and colleagues performed a case-control study of the relationship between coffee consumption and postmenopausal breast cancer. They drew participants from a population-based study of women who were ages 50 to 74, born in Sweden, and residents of the country during 1993 to 1995.
The analysis comprised 2,818 postmenopausal breast cancer patients and 3,111 age-matched controls.
The authors also performed validation analyses based on postmenopausal women who participated in a German case-control study of breast cancer. The analysis included 3,464 patients with breast cancer and 6,657 age-matched controls.
Participants in both studies provided detailed information about breast cancer risk factors, lifestyle factors (such as smoking and diet), and socioeconomic variables.
The initial analysis identified strong associations between breast cancer risk and several variables previously identified in epidemiologic studies: family history of breast cancer, age at menopause, parity, age at first birth, recent body mass index, use of HRT, alcohol consumption, physical activity, and education. Smoking, on the other hand, did not have a significant association with breast cancer risk.
Using data only from the Swedish cohort, the authors performed an age-adjusted analysis, which showed a 20% reduction in the hazard for breast cancer among women who reported drinking more than five cups of coffee daily versus those who averaged less than one cup (P=0.028).
After adjustment for HRT, smoking, education, and alcohol consumption, the effect of coffee consumption on breast cancer risk was no longer significant.
Analyses stratified by tumors' hormone-receptor status resulted in statistically significant reductions in the risk of ER-negative or progesterone (PR)-negative tumors among women who reported drinking more than five cups of coffee daily.
The strongest association between coffee consumption and breast cancer risk was for ER-negative tumors. The combination of ER-negative tumors and heavy coffee consumption resulted in a 57% reduction in the odds for breast cancer (OR 0.43, P=0.0003). Coffee consumption also had a significant association with PR-negative tumors (OR 0.66, P=0.034).
A test for heterogeneity confirmed that the breast cancer benefits of heavy coffee consumption were significantly higher for ER-negative versus ER-positive tumors (P=0.004). The association with PR status no longer remained significant.
Results of the trend analysis in ER-negative cancers led the authors to perform a validation analysis, using data from the German study. The analysis produced a modest overall association between coffee consumption and breast cancer risk, but the association did not achieve statistical significance (OR 0.87, P=0.173).
Analysis of the German data set stratified by cancer subtype confirmed that coffee consumption had the largest protective effect for ER-negative tumors, although the effect was less robust than the one observed in the Swedish cohort and did not achieve statistical significance (OR 0.67, P=0.326).
Published: May 13, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Activate MedPage Today's CME feature and receive free CME credit on medical stories like this oneAction Points
Point out that this study in Sweden found a statistically significant decrease in ER-negative breast cancer among postmenopausal women who had a high daily intake of coffee.
Note that the study is subject to residual confounding by unmeasured variables.
Women who drank at least five cups of coffee daily had a significantly lower risk of postmenopausal breast cancer, an analysis of two large cohort studies suggested.
Overall, the magnitude of the benefit ranged from 20% to more than 50% in unadjusted and adjusted analyses. Analysis of the results by estrogen receptor (ER) status showed that the favorable association pertained only to ER-negative cancers, according to an article published online in Breast Cancer Research.
"Coffee consumption was associated with a strong reduction in breast cancer risk for the ER-negative tumor subtype," Jingmei Li, PhD, of the Karolinska Institute in Stockholm, and co-authors wrote. "This effect was independent of hormone replacement therapy (HRT), smoking, highest education level attained, and average daily alcohol consumption."
"We speculate that coffee might contain compounds that differentially affect breast cancer of different ER subtypes," they added.
Coffee has a paradoxical relationship with breast cancer risk. The beverage's complex mix of caffeine and polyphenols suggests a potential to confer both carcinogenic and chemopreventive characteristics, the authors noted in the introduction to their study.
In general, previous studies have indicated that high coffee consumption might modestly reduce breast cancer risk. However, a meta-analysis of more than 500 reports about coffee's relationship to several types of cancer showed no association with breast cancer (Nutr Cancer 2010; 62: 271-283).
In an effort to add information to the knowledge base, Li and colleagues performed a case-control study of the relationship between coffee consumption and postmenopausal breast cancer. They drew participants from a population-based study of women who were ages 50 to 74, born in Sweden, and residents of the country during 1993 to 1995.
The analysis comprised 2,818 postmenopausal breast cancer patients and 3,111 age-matched controls.
The authors also performed validation analyses based on postmenopausal women who participated in a German case-control study of breast cancer. The analysis included 3,464 patients with breast cancer and 6,657 age-matched controls.
Participants in both studies provided detailed information about breast cancer risk factors, lifestyle factors (such as smoking and diet), and socioeconomic variables.
The initial analysis identified strong associations between breast cancer risk and several variables previously identified in epidemiologic studies: family history of breast cancer, age at menopause, parity, age at first birth, recent body mass index, use of HRT, alcohol consumption, physical activity, and education. Smoking, on the other hand, did not have a significant association with breast cancer risk.
Using data only from the Swedish cohort, the authors performed an age-adjusted analysis, which showed a 20% reduction in the hazard for breast cancer among women who reported drinking more than five cups of coffee daily versus those who averaged less than one cup (P=0.028).
After adjustment for HRT, smoking, education, and alcohol consumption, the effect of coffee consumption on breast cancer risk was no longer significant.
Analyses stratified by tumors' hormone-receptor status resulted in statistically significant reductions in the risk of ER-negative or progesterone (PR)-negative tumors among women who reported drinking more than five cups of coffee daily.
The strongest association between coffee consumption and breast cancer risk was for ER-negative tumors. The combination of ER-negative tumors and heavy coffee consumption resulted in a 57% reduction in the odds for breast cancer (OR 0.43, P=0.0003). Coffee consumption also had a significant association with PR-negative tumors (OR 0.66, P=0.034).
A test for heterogeneity confirmed that the breast cancer benefits of heavy coffee consumption were significantly higher for ER-negative versus ER-positive tumors (P=0.004). The association with PR status no longer remained significant.
Results of the trend analysis in ER-negative cancers led the authors to perform a validation analysis, using data from the German study. The analysis produced a modest overall association between coffee consumption and breast cancer risk, but the association did not achieve statistical significance (OR 0.87, P=0.173).
Analysis of the German data set stratified by cancer subtype confirmed that coffee consumption had the largest protective effect for ER-negative tumors, although the effect was less robust than the one observed in the Swedish cohort and did not achieve statistical significance (OR 0.67, P=0.326).
Subscribe to:
Comments (Atom)
Posts
