Parents concerned about their teens' involvement in risky and criminal behavior have traditionally involved their kids in sports, church and community activities. Do those activities really help prevent risky behaviors in youth? And do the activities affect boys and girls differently?
Previous research has shown that participating in extracurricular activities protects young men and women from risky behaviors and delinquency. This theory was confirmed in a recent study from researchers at Northeastern University’s College of Criminal Justice, but the results also offered a different perspective on how the same activities affect young men and women differently.
While it was previously believed that participation in sports would decrease delinquency in boys, it actually did not have a significant protective effect. However, the reverse was true for girls, whose risk for delinquent behavior was reduced significantly if they took part in sports. Other activities, such as church and after-school community activities, decreased the risk of delinquency in boys, but not for girls.
“This study set out to identify the factors that lead young men and women to fall into serious delinquency and risky behaviors,” said Sean Varano, Assistant Professor of Criminal Justice at Northeastern. “We know that girls and boys have a number of different experiences as they mature, and it is important to understand those differences so that informed decisions can be made on how to protect them.”
The study, completed by Sean Varano, Ph.D., Amy Farrell, Ph.D., both from Northeastern, and Jeb Booth, Ph.D., formerly of Northeastern, examined the self-reported data from 1,400 teens from an upper middle class suburban neighborhood. By looking at both young men and women independently of one another, examining the social controls (parental, academic, etc.) and bonds developed inside the home, in the classroom and during extracurricular activities, it has become clear that they respond differently to certain social controls and activities.
Involvement in church and nonschool activities, for both young men and women, significantly protected them from serious delinquent behavior, which includes fighting, carrying a weapon or violence. However, it did not protect them from risky behavior, such as drinking, smoking or drunk driving.
The researchers also found that how students feel about their school environment also impact their risk of delinquent and risky behavior. Students who view their academic environment as positive are less like to be involved in serious delinquency or risky behavior. The converse is also true – when students feel negatively about their school, they are more likely to exhibit negative behavior. “The fact that this idea was confirmed by our research shows that positive and negative school environments are important for both urban and suburban schools,” said Amy Farrell, Principal Research Scientist and Associate Director of the Institute on Race and Justice at Northeastern.
This study also indicated that a “tipping point” may exist, a point at which too much involvement in extracurricular activities could actually increase levels of risky behavior and serious delinquency. What this may suggest is that the lack of time spent with parents and family might intensify the negative peer influences that the students are exposed to.
“The data clearly shows the need for a balance in students’ lives to best protect them from serious delinquency and risky behaviors,” added Varano. “With continued gender-specific research, better programs can be implemented with the goal of improving the school environment and reducing the incidence of risky behavior and delinquency for all students.”
The Crime & Delinquency article, "Social Control, Serious Delinquency, and Risky Behavior: A Gendered Analysis," written by Jeb A. Booth, Ph.D., formerly of Northeastern, Amy Farrell, Ph.D., and Sean P. Varano, Ph.D., both currently at Northeastern University.
Wednesday, 23 April 2008
New Research Dispels Myth That Cigarettes Make Teenage Girls Thinner, But Smoking May Stunt Growth Of Teenage Boys
New research from the Université de Montréal, funded by the Canadian Cancer Society, shows that teenage girls who smoke cigarettes are no more likely to lose weight than girls who don’t smoke, dispelling a commonly-held belief.
In addition, boys who smoke cigarettes show a decrease in height as well as body mass index (BMI). These findings could have important public health implications, especially since many young girls cite weight control—or the desire to be runway model thin—as a reason for taking up smoking.
The findings, published online in the journal Annals of Epidemiology, are based on data collected from the Nicotine Dependence in Teens study (NDIT). Researchers collected detailed information every three months, over a five-year period, from 1,293 Montreal teens between the ages of 12 and 17.
The research team, led by researcher Dr. Jennifer O’Loughlin at the Université de Montréal, measured the teens’ height, weight, and tricep skinfold thickness. They also gathered information on many other variables, such as levels of physical activity, dietary habits, and teens’ worry about weight.
The study shows that a boy who smokes 10 cigarettes a day from age 12 to 17 will be about an inch shorter than a boy who does not smoke at all. “We were surprised to find that there was no link between smoking and weight among teen girls because it’s something that many of us take for granted,” said Dr. O’Loughlin. “We can only hope that girls will think twice about taking up smoking now, if weight loss is one of their goals.”
Dr. O’Loughlin said teenage boys’ growth may be stunted by smoking because they generally reach puberty later than girls, and are therefore more likely to still be growing when they start smoking. “Maybe teenage boys will see smoking as a bad decision if they dream of being a quarterback or star basketball player,” said Dr. O’Loughlin.
Dr. Barbara Whylie, CEO of the Canadian Cancer Society, says: “This study has enormous potential to prevent teenagers from taking up smoking and has tremendous implications for public health and tobacco control messaging. We are very proud to have funded such a worthwhile project.”
In addition, boys who smoke cigarettes show a decrease in height as well as body mass index (BMI). These findings could have important public health implications, especially since many young girls cite weight control—or the desire to be runway model thin—as a reason for taking up smoking.
The findings, published online in the journal Annals of Epidemiology, are based on data collected from the Nicotine Dependence in Teens study (NDIT). Researchers collected detailed information every three months, over a five-year period, from 1,293 Montreal teens between the ages of 12 and 17.
The research team, led by researcher Dr. Jennifer O’Loughlin at the Université de Montréal, measured the teens’ height, weight, and tricep skinfold thickness. They also gathered information on many other variables, such as levels of physical activity, dietary habits, and teens’ worry about weight.
The study shows that a boy who smokes 10 cigarettes a day from age 12 to 17 will be about an inch shorter than a boy who does not smoke at all. “We were surprised to find that there was no link between smoking and weight among teen girls because it’s something that many of us take for granted,” said Dr. O’Loughlin. “We can only hope that girls will think twice about taking up smoking now, if weight loss is one of their goals.”
Dr. O’Loughlin said teenage boys’ growth may be stunted by smoking because they generally reach puberty later than girls, and are therefore more likely to still be growing when they start smoking. “Maybe teenage boys will see smoking as a bad decision if they dream of being a quarterback or star basketball player,” said Dr. O’Loughlin.
Dr. Barbara Whylie, CEO of the Canadian Cancer Society, says: “This study has enormous potential to prevent teenagers from taking up smoking and has tremendous implications for public health and tobacco control messaging. We are very proud to have funded such a worthwhile project.”
Overweight Kids Need Less Intensive Exercise For Effective Weight Loss, Study Suggests
Overweight kids are better off doing less intensive exercise if they are to shed the pounds effectively, suggests a study of pubescent boys, published ahead of print in the British Journal of Sports Medicine.
The researchers assessed the rate at which fat was burned (fat oxidation) during graded leg cycling exercises in thirty 12 year old boys, 17 of whom were obese. The others were lean and healthy.
The intensity of the exercises increased every 3.5 minutes, with the aim of finding the level of exercise intensity required to burn off the most fat, known as the “Fat Max.”
The Fat Max is determined by the amount of oxygen breathed in and the amount of carbon dioxide breathed out per minute as the exercise intensity increases, calculated as the VO2 peak.
The results showed that the average values of the VO2 peak for the two groups varied considerably, with the lean boys burning much more fat than the fat boys at higher exercise intensity. Among the lean boys the VO2 peak steadily increased before it began to level off at around 50%, although it was still increasing at 60%. The VO2 peak also increased in the obese boys, reaching the same level as the lean boys at 30%, equating to low intensity exercise.
But it then levelled off, before falling sharply at 50%, equating to moderate intensity exercise.
In other words, obese boys reached their Fat Max at much lower levels of exercise intensity than the lean boys. And more intensive exercise did not burn off more fat for them. The authors suggest that this is because obesity, and the sedentary lifestyle it induces, reduces muscle capacity as well as its requirement for, and ability to use, fat as fuel.
And obesity changes muscle type. Obese people have higher levels of type 2 “fast twitch” muscle fibres, which burn off more carbohydrate. Lean people have a higher proportion of type 1 muscle fibres, which burn off more fat, they add.
The researchers assessed the rate at which fat was burned (fat oxidation) during graded leg cycling exercises in thirty 12 year old boys, 17 of whom were obese. The others were lean and healthy.
The intensity of the exercises increased every 3.5 minutes, with the aim of finding the level of exercise intensity required to burn off the most fat, known as the “Fat Max.”
The Fat Max is determined by the amount of oxygen breathed in and the amount of carbon dioxide breathed out per minute as the exercise intensity increases, calculated as the VO2 peak.
The results showed that the average values of the VO2 peak for the two groups varied considerably, with the lean boys burning much more fat than the fat boys at higher exercise intensity. Among the lean boys the VO2 peak steadily increased before it began to level off at around 50%, although it was still increasing at 60%. The VO2 peak also increased in the obese boys, reaching the same level as the lean boys at 30%, equating to low intensity exercise.
But it then levelled off, before falling sharply at 50%, equating to moderate intensity exercise.
In other words, obese boys reached their Fat Max at much lower levels of exercise intensity than the lean boys. And more intensive exercise did not burn off more fat for them. The authors suggest that this is because obesity, and the sedentary lifestyle it induces, reduces muscle capacity as well as its requirement for, and ability to use, fat as fuel.
And obesity changes muscle type. Obese people have higher levels of type 2 “fast twitch” muscle fibres, which burn off more carbohydrate. Lean people have a higher proportion of type 1 muscle fibres, which burn off more fat, they add.
Children Fed Diet of Poor Nutrition on Saturday Morning Television
Nine out of ten food advertisements shown during Saturday morning children's television programming are for foods of poor nutritional quality, according to researchers at the Center for Science in the Public Interest and the University of Minnesota.
During a sample of 27.5 hours of shows aimed at pre-school and elementary school-aged children, 91 percent of food ads were for foods or beverages high in fat, sodium or added sugars or were low in nutrients, according to the study. Forty-nine percent of the 4.08 hours of advertisements shown were for food (281 food ads out of 571 total). The sample, taken from a 2005 review by the Institute of Medicine of the National Academies, included major broadcast and cable networks that had Saturday morning programming.
The most commonly advertised food categories were ready-to-eat breakfast cereals and cereal bars (27 percent of all ads), restaurants (19 percent) and snack foods (18 percent). Of the 281 food ads, 59 percent were for products that exceeded criteria for added sugars, according to the study. About one in five foods advertised exceeded other guidelines, including total fat, saturated plus trans fat and sodium. The majority of advertised foods (84 percent) met the criteria for vitamins and minerals, often as a result of fortification. None of the 27 beverage ads met the study's nutrition standards.
The researchers conclude: "The findings indicate that the foods that food and nutrition professionals encourage children to eat more of, such as fruits, vegetables, low-fat dairy products and whole grains, are seldom encouraged in advertisements shown during children's Saturday morning television programming. Instead, most advertisements promote...foods high in fat, sugars or sodium, or low in nutrients."
This research was published in the April 2008 issue of the Journal of the American Dietetic Association.
During a sample of 27.5 hours of shows aimed at pre-school and elementary school-aged children, 91 percent of food ads were for foods or beverages high in fat, sodium or added sugars or were low in nutrients, according to the study. Forty-nine percent of the 4.08 hours of advertisements shown were for food (281 food ads out of 571 total). The sample, taken from a 2005 review by the Institute of Medicine of the National Academies, included major broadcast and cable networks that had Saturday morning programming.
The most commonly advertised food categories were ready-to-eat breakfast cereals and cereal bars (27 percent of all ads), restaurants (19 percent) and snack foods (18 percent). Of the 281 food ads, 59 percent were for products that exceeded criteria for added sugars, according to the study. About one in five foods advertised exceeded other guidelines, including total fat, saturated plus trans fat and sodium. The majority of advertised foods (84 percent) met the criteria for vitamins and minerals, often as a result of fortification. None of the 27 beverage ads met the study's nutrition standards.
The researchers conclude: "The findings indicate that the foods that food and nutrition professionals encourage children to eat more of, such as fruits, vegetables, low-fat dairy products and whole grains, are seldom encouraged in advertisements shown during children's Saturday morning television programming. Instead, most advertisements promote...foods high in fat, sugars or sodium, or low in nutrients."
This research was published in the April 2008 issue of the Journal of the American Dietetic Association.
Short, Long Sleep Duration Is Associated With Future Weight Gain In Adults
Both short and long sleeping times predict an increased risk of future body weight and fat gain in adults, according to a new study. The study, authored by Jean-Philippe Chaput, of Laval University in Quebec, Canada, focused on 276 adults between 21-64 years of age, whose body composition measurements and self-reported sleep duration were determined. Changes in fatty indices were compared between short (five to six hours), average (seven to eight hours) and long (nine to 10 hours) duration sleeper groups.
According to the results, after adjustment for age, sex, and baseline body mass index, short duration sleepers gained 1.98 kg more and long duration sleepers gained 1.58 kg more than did average duration sleepers over six years.
Short and long duration sleepers were 35 percent and 25 percent more likely to experience a 5 kg weight gain, respectively, as compared with average duration sleepers over six years. The risk of developing obesity was elevated for short and long duration sleepers as compared with average duration sleepers, with 27 percent and 21 percent increases in risk, respectively.
"Our study provides evidence that both short and long sleeping times predict an increased risk of future body weight and fat gain in adults. Furthermore, these results emphasize the need to add sleep duration to the list of environmental factors that are prevalent in our society and that contribute to weight gain and obesity. Since preventing obesity is important, a pragmatic approach adding sleep hygiene advice to encouragement towards a healthy diet and physical activity may help manage the obesity epidemic," said Chaput.
It is recommended that adults get between seven and eight hours of nightly sleep.
The American Academy of Sleep Medicine offers the following tips on how to get a good night's sleep:
Follow a consistent bedtime routine.
Establish a relaxing setting at bedtime.
Get a full night's sleep every night.
Avoid foods or drinks that contain caffeine, as well as any medicine that has a stimulant, prior to bedtime.
Do not bring your worries to bed with you.
Do not go to bed hungry, but don't eat a big meal before bedtime either.
Avoid any rigorous exercise within six hours of your bedtime.
Make your bedroom quiet, dark and a little bit cool.
Get up at the same time every morning.
The article "The Association Between Sleep Duration and Weight Gain in Adults: A 6-Year Prospective Study from the Quebec Family Study" was published in the April 1 issue of the journal Sleep.
According to the results, after adjustment for age, sex, and baseline body mass index, short duration sleepers gained 1.98 kg more and long duration sleepers gained 1.58 kg more than did average duration sleepers over six years.
Short and long duration sleepers were 35 percent and 25 percent more likely to experience a 5 kg weight gain, respectively, as compared with average duration sleepers over six years. The risk of developing obesity was elevated for short and long duration sleepers as compared with average duration sleepers, with 27 percent and 21 percent increases in risk, respectively.
"Our study provides evidence that both short and long sleeping times predict an increased risk of future body weight and fat gain in adults. Furthermore, these results emphasize the need to add sleep duration to the list of environmental factors that are prevalent in our society and that contribute to weight gain and obesity. Since preventing obesity is important, a pragmatic approach adding sleep hygiene advice to encouragement towards a healthy diet and physical activity may help manage the obesity epidemic," said Chaput.
It is recommended that adults get between seven and eight hours of nightly sleep.
The American Academy of Sleep Medicine offers the following tips on how to get a good night's sleep:
Follow a consistent bedtime routine.
Establish a relaxing setting at bedtime.
Get a full night's sleep every night.
Avoid foods or drinks that contain caffeine, as well as any medicine that has a stimulant, prior to bedtime.
Do not bring your worries to bed with you.
Do not go to bed hungry, but don't eat a big meal before bedtime either.
Avoid any rigorous exercise within six hours of your bedtime.
Make your bedroom quiet, dark and a little bit cool.
Get up at the same time every morning.
The article "The Association Between Sleep Duration and Weight Gain in Adults: A 6-Year Prospective Study from the Quebec Family Study" was published in the April 1 issue of the journal Sleep.
Changing School Environment Curbs Weight Gain In Children, Study Shows
Small changes in schools lead to big results when it comes to preventing childhood obesity, according to a study published in the April issue of Pediatrics. The school-based intervention, which reduced the incidence of overweight by 50 percent, offers a potential means of preventing childhood weight gain and obesity on a large scale.
“The increasing prevalence and serious consequences of childhood obesity have pushed us to find solutions that go beyond the clinic and reach greater numbers of children,” said lead author Gary Foster, Ph.D., director of the Center for Obesity Research and Education at Temple University. “We focused on school because children spend most of their lives there and eat at least one if not two meals there.”
The two-year study was conducted in 10 K-8 Philadelphia schools. Half the schools implemented a multi-faceted nutrition policy, including social marketing and family outreach, which was developed by The Food Trust, a non-profit organization committed to ensuring that everyone has access to affordable, nutritious food.
“We incorporated healthy eating into every part of the school day in order to have a greater impact on the students,” said Sandy Sherman, Ed.D., director of nutrition education at The Food Trust. “The intervention fundamentally changed the school environment.”
The other five schools served as a comparison. The study focused on 1,349 students in grades 4 through 6, and followed them for a two-year period, measuring weight, height and physical activity before and after.
The intervention, also called the School Nutrition Policy Initiative, included the following components: school self-assessment, nutrition education, nutrition policy, social marketing and parent outreach.
Nutrition policy
Soda was replaced with water, 100 percent fruit juice and low-fat milk. Snacks were capped at 7 grams of total fat, 2 grams of saturated fat, 360 milligrams of sodium and 15 grams of sugar per serving. Candy was eliminated from the school premises.
Nutrition education
Teachers received 10 hours of training in teaching nutrition, and students received 50 hours of nutrition education over the course of the year.
Social marketing
Kids were rewarded for healthy snacking and encouraged to save their appetites for healthy meals. Nutritious snacks and drinks earned them raffle tickets to win prizes.
Family outreach
Nutrition educators encouraged parents and students to purchase healthy snacks. Students were challenged to be less sedentary and more physically active, and to eat more fruits and vegetables.
Only 7.5 percent of children became overweight in intervention schools, compared with 15 percent of children who became overweight in comparison schools. The intervention was even more effective in African American students, who were less likely to be overweight than those in the comparison schools after two years.
The results are particularly interesting for urban schools, where rates of childhood obesity are disproportionately higher than in suburban areas and greatly affected by the surrounding environment.
“In some inner-city neighborhoods, it’s safer to stay inside after school than to go outside and play. When money is tight, it’s cheaper to feed your kids convenience foods, which are usually higher in fat and calories. Multiple environmental factors are responsible for the childhood obesity epidemic,” said Foster.
Despite the success of the interventions, the fact that 7.5 percent of children in School Nutrition Policy Initiative schools still gained weight over the two-year period suggests that stronger or additional interventions are needed, such as more time spent on physical education, more aggressive nutrition policies, and interventions that target the environment outside of schools.
The researchers also recommend that prevention programs begin even earlier than 4th grade, as the prevalence of overweight children (BMI above the 85th percentile) in grades 4 through 6 is already high at 41.7 percent.
Temple and The Food Trust are currently working together on a corner store initiative, designed to improve the nutrition of food and snacks for sale at neighborhood stores.
“A Policy-Based School Intervention to Prevent Overweight and Obesity,” April 2008, Pediatrics, by Gary D. Foster, PhD, Sandy Sherman, Kelley E. Borradaile, Karen M. Grundy, Stephanie S. Vander Veur, Joan Nachmani, Allison Karpyn, Shiriki Kumanyika, Justine Shults.
“The increasing prevalence and serious consequences of childhood obesity have pushed us to find solutions that go beyond the clinic and reach greater numbers of children,” said lead author Gary Foster, Ph.D., director of the Center for Obesity Research and Education at Temple University. “We focused on school because children spend most of their lives there and eat at least one if not two meals there.”
The two-year study was conducted in 10 K-8 Philadelphia schools. Half the schools implemented a multi-faceted nutrition policy, including social marketing and family outreach, which was developed by The Food Trust, a non-profit organization committed to ensuring that everyone has access to affordable, nutritious food.
“We incorporated healthy eating into every part of the school day in order to have a greater impact on the students,” said Sandy Sherman, Ed.D., director of nutrition education at The Food Trust. “The intervention fundamentally changed the school environment.”
The other five schools served as a comparison. The study focused on 1,349 students in grades 4 through 6, and followed them for a two-year period, measuring weight, height and physical activity before and after.
The intervention, also called the School Nutrition Policy Initiative, included the following components: school self-assessment, nutrition education, nutrition policy, social marketing and parent outreach.
Nutrition policy
Soda was replaced with water, 100 percent fruit juice and low-fat milk. Snacks were capped at 7 grams of total fat, 2 grams of saturated fat, 360 milligrams of sodium and 15 grams of sugar per serving. Candy was eliminated from the school premises.
Nutrition education
Teachers received 10 hours of training in teaching nutrition, and students received 50 hours of nutrition education over the course of the year.
Social marketing
Kids were rewarded for healthy snacking and encouraged to save their appetites for healthy meals. Nutritious snacks and drinks earned them raffle tickets to win prizes.
Family outreach
Nutrition educators encouraged parents and students to purchase healthy snacks. Students were challenged to be less sedentary and more physically active, and to eat more fruits and vegetables.
Only 7.5 percent of children became overweight in intervention schools, compared with 15 percent of children who became overweight in comparison schools. The intervention was even more effective in African American students, who were less likely to be overweight than those in the comparison schools after two years.
The results are particularly interesting for urban schools, where rates of childhood obesity are disproportionately higher than in suburban areas and greatly affected by the surrounding environment.
“In some inner-city neighborhoods, it’s safer to stay inside after school than to go outside and play. When money is tight, it’s cheaper to feed your kids convenience foods, which are usually higher in fat and calories. Multiple environmental factors are responsible for the childhood obesity epidemic,” said Foster.
Despite the success of the interventions, the fact that 7.5 percent of children in School Nutrition Policy Initiative schools still gained weight over the two-year period suggests that stronger or additional interventions are needed, such as more time spent on physical education, more aggressive nutrition policies, and interventions that target the environment outside of schools.
The researchers also recommend that prevention programs begin even earlier than 4th grade, as the prevalence of overweight children (BMI above the 85th percentile) in grades 4 through 6 is already high at 41.7 percent.
Temple and The Food Trust are currently working together on a corner store initiative, designed to improve the nutrition of food and snacks for sale at neighborhood stores.
“A Policy-Based School Intervention to Prevent Overweight and Obesity,” April 2008, Pediatrics, by Gary D. Foster, PhD, Sandy Sherman, Kelley E. Borradaile, Karen M. Grundy, Stephanie S. Vander Veur, Joan Nachmani, Allison Karpyn, Shiriki Kumanyika, Justine Shults.
Teens Who Have TV In Their Bedroom Are Less Likely To Engage In Healthy Habits, Study Shows
University of Minnesota School of Public Health researchers have found that older adolescents who have a bedroom television are less likely to engage in healthy activities such as exercising, eating fruits or vegetables, and enjoying family meals. They also consumed larger quantities of sweetened beverages and fast food, were categorized as heavy TV watchers, and read or studied less than teens without TVs in their bedrooms.
"The American Academy of Pediatrics recommends that parents remove television sets from their children's bedrooms. Despite this recommendation, almost two-thirds of our sample had a bedroom TV, which appears to be a factor for less than optimal behavior," said Daheia Barr-Anderson, Ph.D., M.S.P.H., first author of the study.
A study group of 781 socioeconomically and ethnically diverse teens participating in the School of Public Health Project Eating Among Teens (EAT) study reported on their television viewing habits, study habits, grades, diet, exercise habits, and family connectedness. Nearly two-thirds of the participants had a television in their bedroom or sleeping area, and those who did watched four to five more hours of television each week.
Girls with a TV in their bedrooms spent less time in vigorous activity each week than girls without TVs in their rooms (1.8 versus 2.5 hours). They also ate fewer vegetables (1.7 versus 2 servings per day), and had fewer family meals (2.9 versus 3.7 meals per week). Boys with TVs in their rooms not only had lower fruit intake (1.7 versus 2.2) and fewer family meals (2.9 versus 3.6), they also had a lower grade point average compared with their counterparts with no TVs in the bedroom (2.6 versus 2.9).
Barr-Anderson suggests that the first step parents can take to help their teens decrease unhealthy behaviors is to keep, or remove, a TV from the bedroom of their teen. Dianne Neumark-Sztainer, Ph.D., principal investigator of Project EAT notes, "Our findings suggest the importance of not having a television in a child's bedroom. When families upgrade their living room television, they may want to resist the temptation to put the older television set in their children's bedroom."
This study was supported by a grant from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services, and by an Adolescent Health Protection Research Training grant from the Centers for Disease Control and Prevention, Department of Health and Human Services.
The study, "Characteristics Associated With Older Adolescents Who Have a Television in Their Bedrooms," will be published in the May edition of Pediatrics, the official journal of the American Academy of Pediatrics.
"The American Academy of Pediatrics recommends that parents remove television sets from their children's bedrooms. Despite this recommendation, almost two-thirds of our sample had a bedroom TV, which appears to be a factor for less than optimal behavior," said Daheia Barr-Anderson, Ph.D., M.S.P.H., first author of the study.
A study group of 781 socioeconomically and ethnically diverse teens participating in the School of Public Health Project Eating Among Teens (EAT) study reported on their television viewing habits, study habits, grades, diet, exercise habits, and family connectedness. Nearly two-thirds of the participants had a television in their bedroom or sleeping area, and those who did watched four to five more hours of television each week.
Girls with a TV in their bedrooms spent less time in vigorous activity each week than girls without TVs in their rooms (1.8 versus 2.5 hours). They also ate fewer vegetables (1.7 versus 2 servings per day), and had fewer family meals (2.9 versus 3.7 meals per week). Boys with TVs in their rooms not only had lower fruit intake (1.7 versus 2.2) and fewer family meals (2.9 versus 3.6), they also had a lower grade point average compared with their counterparts with no TVs in the bedroom (2.6 versus 2.9).
Barr-Anderson suggests that the first step parents can take to help their teens decrease unhealthy behaviors is to keep, or remove, a TV from the bedroom of their teen. Dianne Neumark-Sztainer, Ph.D., principal investigator of Project EAT notes, "Our findings suggest the importance of not having a television in a child's bedroom. When families upgrade their living room television, they may want to resist the temptation to put the older television set in their children's bedroom."
This study was supported by a grant from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services, and by an Adolescent Health Protection Research Training grant from the Centers for Disease Control and Prevention, Department of Health and Human Services.
The study, "Characteristics Associated With Older Adolescents Who Have a Television in Their Bedrooms," will be published in the May edition of Pediatrics, the official journal of the American Academy of Pediatrics.
Macadamia Nuts Can Be Included In Heart Healthy Diet, Study Suggests
Macadamia nuts included in a heart healthy diet reduced low-density cholesterol (bad cholesterol) and should be included among nuts with qualified health claims, according to researchers.
"We looked at macadamia nuts because they are not currently included in the health claim for tree nuts, while other tree nuts are currently recommended as part of a heart healthy diet," says Dr. Amy E. Griel, a recent Penn State Ph.D. recipient in nutrition and now senior nutrition scientist at The Hershey Company.* "Macadamia nuts have higher levels of monosaturated fats, like those found in olive oil compared with other tree nuts."
Along with Brazil nuts and cashews, macadamia nuts are not included in the U.S. Food and Drug Administration's list of nuts with qualified health claims because the cut-off point is 4 grams of saturated fat per 50 grams of nuts. Macadamia nuts have 6 grams of saturated fat per 50 grams, cashew nuts have 4.6 grams and Brazil nuts have 7.6 grams of saturated fat per 50 grams of nuts.
"Epidemiological studies showed that people who are frequent nut consumers have decreased risk of heart disease," says Penny Kris-Etherton, co-author and distinguished professor of nutritional sciences.
The researchers used a controlled feeding study to compare a heart-healthy diet with 1.5 ounces -- a small handful -- of macadamia nuts to a standard American diet. The participants had slightly elevated cholesterol levels, normal blood pressure and were not taking lipid-lowering drugs. Researchers randomly assigned participants to either the macadamia nut diet or the standard American diet and provided all meals for the participants for five weeks. The participants then switched diets and continued eating only food provided by the researchers for another five weeks.
The Healthy Heart diet with macadamia nuts did reduce total cholesterol, low-density lipoprotein cholesterol and triglyceride levels compared with the standard American diet. The researchers reported in the current issue of the Journal of Nutrition, that the macadamia nuts reduced total cholesterol by 9.4 percent and low-density lipoprotein by 8.9 percent.
Individual calorie levels were used for each participant so that they did not gain or lose weight during the study. Both diets were matched for total fat, containing 33 percent calories from total fat. The Heart Healthy diet with macadamia nuts had 7 percent saturated fat, 18 percent monosaturated fat and 5 percent polyunsaturated fat. The standard American diet had 13 percent saturated fat, 11 percent monosaturated fat and 5 percent saturated fat.
"We found that the reduction in LDL or bad cholesterol we observed was greater than would be predicted by just the healthy fats in the nuts alone," says Griel. "This indicates that there is something else in the nuts that helps lower cholesterol."
The macadamia nut diet included macadamia nuts as a snack, mixed into meals, as a salad topping and in cookies and muffins. The total fat was the same in both diets. Macadamia nuts were substituted for other sources of fat and protein in the diet. Switching skim milk for 2 percent milk and adding some macadamia nuts kept fat levels even.
"I think the bottom line is that Macadamia nuts probably should be included in the list of nuts to have a qualified health claim," says Kris-Etherton.
Researchers on this study included Griel; Kris-Etherton: Deborah M. Bagshaw, research assistant, nutrition; Amy M. Cifelli, research scientist; Yumei Cao, graduate student in nutrition, Penn State; and Bruce Holub, University of Guelph.
*This study was supported by The Hershey Company, owners of Mauna Loa Macadamia, with partial support from National Institutes of Health.
"We looked at macadamia nuts because they are not currently included in the health claim for tree nuts, while other tree nuts are currently recommended as part of a heart healthy diet," says Dr. Amy E. Griel, a recent Penn State Ph.D. recipient in nutrition and now senior nutrition scientist at The Hershey Company.* "Macadamia nuts have higher levels of monosaturated fats, like those found in olive oil compared with other tree nuts."
Along with Brazil nuts and cashews, macadamia nuts are not included in the U.S. Food and Drug Administration's list of nuts with qualified health claims because the cut-off point is 4 grams of saturated fat per 50 grams of nuts. Macadamia nuts have 6 grams of saturated fat per 50 grams, cashew nuts have 4.6 grams and Brazil nuts have 7.6 grams of saturated fat per 50 grams of nuts.
"Epidemiological studies showed that people who are frequent nut consumers have decreased risk of heart disease," says Penny Kris-Etherton, co-author and distinguished professor of nutritional sciences.
The researchers used a controlled feeding study to compare a heart-healthy diet with 1.5 ounces -- a small handful -- of macadamia nuts to a standard American diet. The participants had slightly elevated cholesterol levels, normal blood pressure and were not taking lipid-lowering drugs. Researchers randomly assigned participants to either the macadamia nut diet or the standard American diet and provided all meals for the participants for five weeks. The participants then switched diets and continued eating only food provided by the researchers for another five weeks.
The Healthy Heart diet with macadamia nuts did reduce total cholesterol, low-density lipoprotein cholesterol and triglyceride levels compared with the standard American diet. The researchers reported in the current issue of the Journal of Nutrition, that the macadamia nuts reduced total cholesterol by 9.4 percent and low-density lipoprotein by 8.9 percent.
Individual calorie levels were used for each participant so that they did not gain or lose weight during the study. Both diets were matched for total fat, containing 33 percent calories from total fat. The Heart Healthy diet with macadamia nuts had 7 percent saturated fat, 18 percent monosaturated fat and 5 percent polyunsaturated fat. The standard American diet had 13 percent saturated fat, 11 percent monosaturated fat and 5 percent saturated fat.
"We found that the reduction in LDL or bad cholesterol we observed was greater than would be predicted by just the healthy fats in the nuts alone," says Griel. "This indicates that there is something else in the nuts that helps lower cholesterol."
The macadamia nut diet included macadamia nuts as a snack, mixed into meals, as a salad topping and in cookies and muffins. The total fat was the same in both diets. Macadamia nuts were substituted for other sources of fat and protein in the diet. Switching skim milk for 2 percent milk and adding some macadamia nuts kept fat levels even.
"I think the bottom line is that Macadamia nuts probably should be included in the list of nuts to have a qualified health claim," says Kris-Etherton.
Researchers on this study included Griel; Kris-Etherton: Deborah M. Bagshaw, research assistant, nutrition; Amy M. Cifelli, research scientist; Yumei Cao, graduate student in nutrition, Penn State; and Bruce Holub, University of Guelph.
*This study was supported by The Hershey Company, owners of Mauna Loa Macadamia, with partial support from National Institutes of Health.
Macadamia Nuts Can Be Included In Heart Healthy Diet, Study Suggests
Macadamia nuts included in a heart healthy diet reduced low-density cholesterol (bad cholesterol) and should be included among nuts with qualified health claims, according to researchers.
"We looked at macadamia nuts because they are not currently included in the health claim for tree nuts, while other tree nuts are currently recommended as part of a heart healthy diet," says Dr. Amy E. Griel, a recent Penn State Ph.D. recipient in nutrition and now senior nutrition scientist at The Hershey Company.* "Macadamia nuts have higher levels of monosaturated fats, like those found in olive oil compared with other tree nuts."
Along with Brazil nuts and cashews, macadamia nuts are not included in the U.S. Food and Drug Administration's list of nuts with qualified health claims because the cut-off point is 4 grams of saturated fat per 50 grams of nuts. Macadamia nuts have 6 grams of saturated fat per 50 grams, cashew nuts have 4.6 grams and Brazil nuts have 7.6 grams of saturated fat per 50 grams of nuts.
"Epidemiological studies showed that people who are frequent nut consumers have decreased risk of heart disease," says Penny Kris-Etherton, co-author and distinguished professor of nutritional sciences.
The researchers used a controlled feeding study to compare a heart-healthy diet with 1.5 ounces -- a small handful -- of macadamia nuts to a standard American diet. The participants had slightly elevated cholesterol levels, normal blood pressure and were not taking lipid-lowering drugs. Researchers randomly assigned participants to either the macadamia nut diet or the standard American diet and provided all meals for the participants for five weeks. The participants then switched diets and continued eating only food provided by the researchers for another five weeks.
The Healthy Heart diet with macadamia nuts did reduce total cholesterol, low-density lipoprotein cholesterol and triglyceride levels compared with the standard American diet. The researchers reported in the current issue of the Journal of Nutrition, that the macadamia nuts reduced total cholesterol by 9.4 percent and low-density lipoprotein by 8.9 percent.
Individual calorie levels were used for each participant so that they did not gain or lose weight during the study. Both diets were matched for total fat, containing 33 percent calories from total fat. The Heart Healthy diet with macadamia nuts had 7 percent saturated fat, 18 percent monosaturated fat and 5 percent polyunsaturated fat. The standard American diet had 13 percent saturated fat, 11 percent monosaturated fat and 5 percent saturated fat.
"We found that the reduction in LDL or bad cholesterol we observed was greater than would be predicted by just the healthy fats in the nuts alone," says Griel. "This indicates that there is something else in the nuts that helps lower cholesterol."
The macadamia nut diet included macadamia nuts as a snack, mixed into meals, as a salad topping and in cookies and muffins. The total fat was the same in both diets. Macadamia nuts were substituted for other sources of fat and protein in the diet. Switching skim milk for 2 percent milk and adding some macadamia nuts kept fat levels even.
"I think the bottom line is that Macadamia nuts probably should be included in the list of nuts to have a qualified health claim," says Kris-Etherton.
Researchers on this study included Griel; Kris-Etherton: Deborah M. Bagshaw, research assistant, nutrition; Amy M. Cifelli, research scientist; Yumei Cao, graduate student in nutrition, Penn State; and Bruce Holub, University of Guelph.
*This study was supported by The Hershey Company, owners of Mauna Loa Macadamia, with partial support from National Institutes of Health.
"We looked at macadamia nuts because they are not currently included in the health claim for tree nuts, while other tree nuts are currently recommended as part of a heart healthy diet," says Dr. Amy E. Griel, a recent Penn State Ph.D. recipient in nutrition and now senior nutrition scientist at The Hershey Company.* "Macadamia nuts have higher levels of monosaturated fats, like those found in olive oil compared with other tree nuts."
Along with Brazil nuts and cashews, macadamia nuts are not included in the U.S. Food and Drug Administration's list of nuts with qualified health claims because the cut-off point is 4 grams of saturated fat per 50 grams of nuts. Macadamia nuts have 6 grams of saturated fat per 50 grams, cashew nuts have 4.6 grams and Brazil nuts have 7.6 grams of saturated fat per 50 grams of nuts.
"Epidemiological studies showed that people who are frequent nut consumers have decreased risk of heart disease," says Penny Kris-Etherton, co-author and distinguished professor of nutritional sciences.
The researchers used a controlled feeding study to compare a heart-healthy diet with 1.5 ounces -- a small handful -- of macadamia nuts to a standard American diet. The participants had slightly elevated cholesterol levels, normal blood pressure and were not taking lipid-lowering drugs. Researchers randomly assigned participants to either the macadamia nut diet or the standard American diet and provided all meals for the participants for five weeks. The participants then switched diets and continued eating only food provided by the researchers for another five weeks.
The Healthy Heart diet with macadamia nuts did reduce total cholesterol, low-density lipoprotein cholesterol and triglyceride levels compared with the standard American diet. The researchers reported in the current issue of the Journal of Nutrition, that the macadamia nuts reduced total cholesterol by 9.4 percent and low-density lipoprotein by 8.9 percent.
Individual calorie levels were used for each participant so that they did not gain or lose weight during the study. Both diets were matched for total fat, containing 33 percent calories from total fat. The Heart Healthy diet with macadamia nuts had 7 percent saturated fat, 18 percent monosaturated fat and 5 percent polyunsaturated fat. The standard American diet had 13 percent saturated fat, 11 percent monosaturated fat and 5 percent saturated fat.
"We found that the reduction in LDL or bad cholesterol we observed was greater than would be predicted by just the healthy fats in the nuts alone," says Griel. "This indicates that there is something else in the nuts that helps lower cholesterol."
The macadamia nut diet included macadamia nuts as a snack, mixed into meals, as a salad topping and in cookies and muffins. The total fat was the same in both diets. Macadamia nuts were substituted for other sources of fat and protein in the diet. Switching skim milk for 2 percent milk and adding some macadamia nuts kept fat levels even.
"I think the bottom line is that Macadamia nuts probably should be included in the list of nuts to have a qualified health claim," says Kris-Etherton.
Researchers on this study included Griel; Kris-Etherton: Deborah M. Bagshaw, research assistant, nutrition; Amy M. Cifelli, research scientist; Yumei Cao, graduate student in nutrition, Penn State; and Bruce Holub, University of Guelph.
*This study was supported by The Hershey Company, owners of Mauna Loa Macadamia, with partial support from National Institutes of Health.
Developmental Changes In Adolescence Raise Men's Heart Disease Risk, Study Shows
Normal developmental changes during the teenage years leave young adult men at higher risk of heart disease than their female counterparts, researchers report in Circulation: Journal of the American Heart Association.
"Women's protective advantage against heart disease starts young," said Antoinette Moran, M.D., lead author of the study and professor and division chief of pediatric endocrinology and diabetes at the University of Minnesota Children's Hospital in Minneapolis.
In adults, a constellation of factors increases the risk of heart disease. They include high blood pressure, smoking, obesity, physical inactivity, abnormal cholesterol levels and insulin resistance (a pre-diabetic condition in which the body can't use insulin effectively).
To track the emergence of these risk factors, researchers followed 507 Minneapolis school children from ages 11 to 19, when they had all reached sexual maturity. Fifty-seven percent of the children were male, 80 percent were white and 20 percent were black.
During the study, the researchers made 996 observations on the group, noting blood pressure, insulin sensitivity (opposite to insulin resistance), body mass index and other body composition measures, blood glucose and cholesterol measurements.
"We wanted to see which risks emerge first and how they relate to one another in normal, healthy school kids without diabetes or other major illnesses," Moran said.
At age 11, boys and girls were similar in their body composition, lipid levels and blood pressure, researchers said.
Boys and girls became heavier during adolescence, increasing in body mass index and waist size. As expected during puberty, changes in body composition differed sharply between genders, with percentage of body fat decreasing in boys and increasing in girls.
During the study, changes in several cardiovascular risk factors or risk markers differed significantly between boys and girls:
Triglycerides (a type of fat in the blood) increased in males and decreased in females.
High-density lipoprotein (HDL or "good") cholesterol decreased in males and increased in females.
Systolic blood pressure (the first number in the blood pressure reading, measuring the pressure when the heart contracts) increased in both, but significantly more in the males.
Insulin resistance, which had been lower in the boys at age 11, steadily increased until the young men at age 19 were more insulin resistant than the women.
Researchers found no gender difference in two other cardiovascular risk factors, total cholesterol and low-density lipoprotein (LDL or "bad") cholesterol.
"By age 19, the boys were at greater cardiovascular risk," Moran said. "This is particularly surprising because we usually think of body fat as associated with cardiovascular risk, and the increasing risk in boys happened at the time in normal development when they were gaining muscle mass and losing fat."
Although girls gained cardiovascular protection when their proportion of body fat was increasing, excess fat is still a cause for concern.
"Obesity trumps all of the other factors and erases any gender-protective effect," Moran said. "Obese boys and girls and men and women all have higher cardiovascular risk."
The researchers said further studies are needed to better understand the development of cardiovascular protection during adolescence.
"That the protection associated with female gender starts young is fascinating and something that we don't understand very well," Moran said. "That this protection emerges during puberty and disappears after menopause suggests that sex hormones give women a protective advantage. There's still a lot that needs to be sorted out in future studies -- estrogen may be protective or testosterone may be harmful."
Moran noted that this is normal physiology and not something that is influenced by lifestyle factors.
"Women's protective advantage against heart disease starts young," said Antoinette Moran, M.D., lead author of the study and professor and division chief of pediatric endocrinology and diabetes at the University of Minnesota Children's Hospital in Minneapolis.
In adults, a constellation of factors increases the risk of heart disease. They include high blood pressure, smoking, obesity, physical inactivity, abnormal cholesterol levels and insulin resistance (a pre-diabetic condition in which the body can't use insulin effectively).
To track the emergence of these risk factors, researchers followed 507 Minneapolis school children from ages 11 to 19, when they had all reached sexual maturity. Fifty-seven percent of the children were male, 80 percent were white and 20 percent were black.
During the study, the researchers made 996 observations on the group, noting blood pressure, insulin sensitivity (opposite to insulin resistance), body mass index and other body composition measures, blood glucose and cholesterol measurements.
"We wanted to see which risks emerge first and how they relate to one another in normal, healthy school kids without diabetes or other major illnesses," Moran said.
At age 11, boys and girls were similar in their body composition, lipid levels and blood pressure, researchers said.
Boys and girls became heavier during adolescence, increasing in body mass index and waist size. As expected during puberty, changes in body composition differed sharply between genders, with percentage of body fat decreasing in boys and increasing in girls.
During the study, changes in several cardiovascular risk factors or risk markers differed significantly between boys and girls:
Triglycerides (a type of fat in the blood) increased in males and decreased in females.
High-density lipoprotein (HDL or "good") cholesterol decreased in males and increased in females.
Systolic blood pressure (the first number in the blood pressure reading, measuring the pressure when the heart contracts) increased in both, but significantly more in the males.
Insulin resistance, which had been lower in the boys at age 11, steadily increased until the young men at age 19 were more insulin resistant than the women.
Researchers found no gender difference in two other cardiovascular risk factors, total cholesterol and low-density lipoprotein (LDL or "bad") cholesterol.
"By age 19, the boys were at greater cardiovascular risk," Moran said. "This is particularly surprising because we usually think of body fat as associated with cardiovascular risk, and the increasing risk in boys happened at the time in normal development when they were gaining muscle mass and losing fat."
Although girls gained cardiovascular protection when their proportion of body fat was increasing, excess fat is still a cause for concern.
"Obesity trumps all of the other factors and erases any gender-protective effect," Moran said. "Obese boys and girls and men and women all have higher cardiovascular risk."
The researchers said further studies are needed to better understand the development of cardiovascular protection during adolescence.
"That the protection associated with female gender starts young is fascinating and something that we don't understand very well," Moran said. "That this protection emerges during puberty and disappears after menopause suggests that sex hormones give women a protective advantage. There's still a lot that needs to be sorted out in future studies -- estrogen may be protective or testosterone may be harmful."
Moran noted that this is normal physiology and not something that is influenced by lifestyle factors.
Prostate Cancer Can Be Halted With Anti-inflammatory And Statin Used In Tandem, Study Suggests
Researchers at Rutgers' Ernest Mario School of Pharmacy have shown that administering a combination of the widely used drugs Celebrex (celecoxib, a nonsteroidal anti-inflammatory drug) and Lipitor (atorvastatin, a cholesterol lowering drug) stops the transition of early prostate cancer to its more aggressive and potentially fatal stage.
Prostate cancer is the second leading cause of cancer death in men in the United States, with more than a quarter-million new cases appearing each year, according to the American Cancer Society. The findings are being presented by Rutgers Professor Xi Zheng at the annual meeting of the American Association for Cancer Research in San Diego, April 14th.
In the early stage of the disease, when it is typically diagnosed, prostate cancer cells depend on androgen hormones, such as testosterone, to grow. Treatment at this stage involves either decreasing the production of the hormone or blocking its actions on the cancer cells.
"Anti-androgen therapy slows the prostate cancer but eventually the cancer becomes androgen-independent, the therapy becomes ineffective and the cancer cells become more aggressive," said Xi Zheng, assistant research professor at Rutgers, The State University of New Jersey, who conducted the study.
"Treatments available for the later stage cancers are not very good," said Allan Conney, director of Rutgers' Susan Lehman Cullman Laboratory for Cancer Research, another researcher on the project. "Oncologists employ classical chemotherapy drugs which are very toxic and don't work all that well."
Zheng and Conney's research objective was to find a way to indefinitely delay the transition to androgen-independence, prolonging the time during which the cancer would be responsive to effective, low-toxicity, anti-hormone therapy.
Zheng explained that their experiments were first conducted on cell cultures in the laboratory, where the researchers tested the effects of the drugs on the growth of prostate cancer cells from four different cell lines. They then moved on to test the drugs on specially bred mice in which prostate cancer tumors were introduced under the skin. Celebrex alone, Lipitor alone, and the two in combination were tested at the lab bench and on the mice.
"A combination of low doses of Lipitor and Celebrex had a more potent inhibiting effect on the formation of later stage tumors than a higher dose of either agent alone," Zheng reported. "The results from our study indicate that a combination of Lipitor and Celebrex may be an effective strategy for the prevention of prostate cancer progression from the first to the second stage."
Zheng also noted that the team is exploring the underlying molecular mechanisms to understand how Lipitor and Celebrex work on prostate cancer, perhaps identifying an important signaling pathway for tumor cell growth that the drugs inhibit.
Conney pointed out that previous experiments reported in the Sept. 15, 2007, issue of Clinical Cancer Research had demonstrated that the Lipitor-Celebrex combination also inhibited the growth of prostate cancer cells in the later androgen-independent stage.
"So if you can affect the early stage and prevent it from becoming the more severe form, that's a good thing. If you can also inhibit the growth of the more severe form, that's also a good thing," Conney said.
Human clinical trials are being planned at the Robert Wood Johnson Medical School of the University of Medicine and Dentistry of New Jersey in New Brunswick.
"If the clinical trials go well, we could have something available in five years, but it would be nice to speed that up," Conney said. "If the trials show that the drug therapy does a good job of preventing the cancer from advancing, we won't need to worry about how to handle the more aggressive later stage cancer.
"This is something we hope is going to save lives," he added.
Prostate cancer is the second leading cause of cancer death in men in the United States, with more than a quarter-million new cases appearing each year, according to the American Cancer Society. The findings are being presented by Rutgers Professor Xi Zheng at the annual meeting of the American Association for Cancer Research in San Diego, April 14th.
In the early stage of the disease, when it is typically diagnosed, prostate cancer cells depend on androgen hormones, such as testosterone, to grow. Treatment at this stage involves either decreasing the production of the hormone or blocking its actions on the cancer cells.
"Anti-androgen therapy slows the prostate cancer but eventually the cancer becomes androgen-independent, the therapy becomes ineffective and the cancer cells become more aggressive," said Xi Zheng, assistant research professor at Rutgers, The State University of New Jersey, who conducted the study.
"Treatments available for the later stage cancers are not very good," said Allan Conney, director of Rutgers' Susan Lehman Cullman Laboratory for Cancer Research, another researcher on the project. "Oncologists employ classical chemotherapy drugs which are very toxic and don't work all that well."
Zheng and Conney's research objective was to find a way to indefinitely delay the transition to androgen-independence, prolonging the time during which the cancer would be responsive to effective, low-toxicity, anti-hormone therapy.
Zheng explained that their experiments were first conducted on cell cultures in the laboratory, where the researchers tested the effects of the drugs on the growth of prostate cancer cells from four different cell lines. They then moved on to test the drugs on specially bred mice in which prostate cancer tumors were introduced under the skin. Celebrex alone, Lipitor alone, and the two in combination were tested at the lab bench and on the mice.
"A combination of low doses of Lipitor and Celebrex had a more potent inhibiting effect on the formation of later stage tumors than a higher dose of either agent alone," Zheng reported. "The results from our study indicate that a combination of Lipitor and Celebrex may be an effective strategy for the prevention of prostate cancer progression from the first to the second stage."
Zheng also noted that the team is exploring the underlying molecular mechanisms to understand how Lipitor and Celebrex work on prostate cancer, perhaps identifying an important signaling pathway for tumor cell growth that the drugs inhibit.
Conney pointed out that previous experiments reported in the Sept. 15, 2007, issue of Clinical Cancer Research had demonstrated that the Lipitor-Celebrex combination also inhibited the growth of prostate cancer cells in the later androgen-independent stage.
"So if you can affect the early stage and prevent it from becoming the more severe form, that's a good thing. If you can also inhibit the growth of the more severe form, that's also a good thing," Conney said.
Human clinical trials are being planned at the Robert Wood Johnson Medical School of the University of Medicine and Dentistry of New Jersey in New Brunswick.
"If the clinical trials go well, we could have something available in five years, but it would be nice to speed that up," Conney said. "If the trials show that the drug therapy does a good job of preventing the cancer from advancing, we won't need to worry about how to handle the more aggressive later stage cancer.
"This is something we hope is going to save lives," he added.
Ovarian Cancer Stem Cells Identified, Characterized
Researchers at Yale School of Medicine have identified, characterized and cloned ovarian cancer stem cells and have shown that these stem cells may be the source of ovarian cancer's recurrence and its resistance to chemotherapy.
"These results bring us closer to more effective and targeted treatment for epithelial ovarian cancer, one of the most lethal forms of cancer," said Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.
Mor presented his findings recently at the annual meeting of the American Association for Cancer Research (AACR) Meeting in San Diego, California.
Cancerous tumors are made up of cells that are both cancerous and non-cancerous. Within cancerous cells, there is a further subclass referred to as cancer stem cells, which can replicate indefinitely.
"Present chemotherapy modalities eliminate the bulk of the tumor cells, but cannot eliminate a core of these cancer stem cells that have a high capacity for renewal," said Mor, who is also a member of the Yale Cancer Center. "Identification of these cells, as we have done here, is the first step in the development of therapeutic modalities."
Mor and colleagues isolated cells from 80 human samples of either peritoneal fluid or solid tumors. The cancer stem cells that were identified were positive for traditional cancer stem cell markers including CD44 and MyD88. These cells also showed a high capacity for repair and self-renewal.
The isolated cells formed tumors 100 percent of the time. Within those tumors, 10 percent of the cells were positive for cancer stem cell marker CD44, while 90 percent were CD44 negative.
Mor and his team were able to isolate and clone the ovarian cancer stem cells. They found that these cells were highly resistant to conventional chemotherapy while the non-cancer stem cells responded to treatment. "Isolating and cloning these cells will lead to development of new treatments to target and eliminate the cancer stem cells and hopefully prevent recurrence," said Mor.
"These results bring us closer to more effective and targeted treatment for epithelial ovarian cancer, one of the most lethal forms of cancer," said Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.
Mor presented his findings recently at the annual meeting of the American Association for Cancer Research (AACR) Meeting in San Diego, California.
Cancerous tumors are made up of cells that are both cancerous and non-cancerous. Within cancerous cells, there is a further subclass referred to as cancer stem cells, which can replicate indefinitely.
"Present chemotherapy modalities eliminate the bulk of the tumor cells, but cannot eliminate a core of these cancer stem cells that have a high capacity for renewal," said Mor, who is also a member of the Yale Cancer Center. "Identification of these cells, as we have done here, is the first step in the development of therapeutic modalities."
Mor and colleagues isolated cells from 80 human samples of either peritoneal fluid or solid tumors. The cancer stem cells that were identified were positive for traditional cancer stem cell markers including CD44 and MyD88. These cells also showed a high capacity for repair and self-renewal.
The isolated cells formed tumors 100 percent of the time. Within those tumors, 10 percent of the cells were positive for cancer stem cell marker CD44, while 90 percent were CD44 negative.
Mor and his team were able to isolate and clone the ovarian cancer stem cells. They found that these cells were highly resistant to conventional chemotherapy while the non-cancer stem cells responded to treatment. "Isolating and cloning these cells will lead to development of new treatments to target and eliminate the cancer stem cells and hopefully prevent recurrence," said Mor.
Immunotherapy: Enlisting The Immune System To Fight Cancer
Researchers are directing the body's immune system to shrink tumors and prevent new ones from forming. Data presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, detail how cellular strategies and new vaccines are changing the cancer treatment landscape.
The first use of a live listeria cancer vaccine in man
Phase I/II trial results have shown that the live Listeria cancer vaccine, Lovaxin C, is safe for humans. In addition, three women in the cervical cancer trial had approximately 20 percent tumor reductions, researchers report.
"We are using Listeria to deliver tumor-specific antigens to the immune system in a manner that results in maximal immune and tumor-clearing response," said John Rothman, Ph.D., vice president of clinical development at Advaxis, which is developing Lovaxin C.
The trial included 15 women with progressive, recurrent or advanced cervical cancer. All patients had failed chemotherapy, radiotherapy or surgery. The women had metastatic disease and most were stage IVb.
Listeria monocytogenes infects antigen presenting cells (APCs) -- "a very special piece of immune real estate," Rothman said. These cells consume foreign invaders and instruct the immune system to attack them. Listeria thrives within APCs and thus directs an immune response.
"We bioengineer Listeria both to attenuate it and to cause it to secrete a tumor-specific antigen fused to a listerial protein, which makes it more effective than Listeria that just secretes the tumor antigen," Rothman said. "By doing this we focus a very strong immune attack against the antigen in question, which is typically specific to a tumor."
"What we're doing is taking a lot of evolution that enabled Listeria to infect human immune systems, and an equal amount of evolution that enables humans to get rid of Listeria once this occurs. We are then co-opting and redirecting all of these complex immune responses and targeting them against cancer," Rothman said.
The researchers divided the patients into three groups of five; each group received two doses of either 1x109, 3.3x109 or 1x1010 units of Listeria at three-week intervals. They administered ampicillin five days after each dose, first intravenously and then orally for 10 days.
Each patient developed flu-like symptoms, including fever, chills and nausea with or without vomiting. In the lower doses, these symptoms were treated with non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) and anti-emetics. Patients in the highest dose group had the same but more severe symptoms.
Rothman used the RECIST criteria to assess the tumors in 13 patients. At the end of the study, five patients had progression of their cancer, seven were stable, and one patient showed a partial response to the therapy. Three of the seven stable patients had tumor reductions of about 20 percent.
The partial response patient -- who was stage IVb at trial initiation -- was given six chemotherapy courses and a radical hysterectomy. Currently, she is tumor- free and her blood tests are normal. Six of the 13 patients are surviving, with a median survival of 424 days. Median survival for all 15 treated patients is 327 days.
CTLA-4 blockade for hormone refractory prostate cancer: dose-dependent induction of CD8+ T cell activation and clinical responses
Blocking CTLA-4, a cellular molecule on lymphocytes that inhibits immune response, produced meaningful clinical benefits in patients with prostate cancer that hadn't responded to hormone therapy, according to researchers.
"CTLA-4 blockade works by removing the brakes on the immune system. Our results show that enhancing immune responses in prostate cancer patients can lead to clinical responses," said Lawrence Fong, M.D., a hematology/oncology researcher at University of California, San Francisco.
In a phase 1 trial in 24 patients with metastatic prostate cancer that was unresponsive to hormone therapy, Fong and colleagues treated groups of three to six patients with increasing intravenous doses of ipilimumab (0.5, 1.5 or 3 mg/kg), a fully human anti-CTLA-4 antibody, on the first day of each 28-day treatment cycle. There were four cycles in the trial. The researchers also gave the patients 250 mg/m2/d of granulocyte-macrophage colony-stimulating factor every day for the first two weeks of each cycle.
Researchers monitored T cell activation and toxicity. They performed prostate-specific antigen (PSA) and radiographic tests at enrollment and throughout treatment to assess clinical response.
Three of the six patients treated with the highest ipilimumab dose (3.0 mg/kg x 4) had confirmed declines in PSA levels of more than 50 percent. One of these patients had a partial response in cancer that had spread to the liver.
The researchers found that activation of lymphocytes occurred primarily in the higher doses. They also could detect lymphocytes targeting proteins expressed by prostate cancer cells in some patients following treatment.
Immune-related side effects -- including skin rash, diarrhea and a deficiency in pituitary hormone production -- were most common in the group receiving the higher ipilimumab doses.
Fong and colleagues will continue to study CTLA-4 blockade. "We are studying higher doses of anti-CTLA-4 antibody and look forward to beginning a larger phase 2 trial in the next three to six months," Fong said.
Dendritic and T cell functions in patients with metastatic hormone-refractory prostate cancer treated with GVAX immunotherapy for prostate cancer and ipilumumab
Researchers have found a promising synergy of two therapies to treat metastatic prostate cancer that is resistant to hormone therapy. In a phase I trial, they observed that a combination of GVAX immunotherapy with ipilimumab lowered prostate-specific antigen (PSA) levels in some patients.
"Higher doses of ipilimumab combined with the GVAX vaccine is showing a lot of success in increasing anti-tumor activity in these patients," said Saskia J.A.M. Santegoets, Ph.D., a researcher in the Department of Pathology and Division of Immunotherapy at the Vrije Universiteit Medical Center in the Netherlands. "We're encouraged by the results of this phase I trial and expect ongoing analyses to yield more valuable data about the GVAX/ ipilimumab combination."
In this trial, the vaccine was administered with escalating doses of anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab. Researchers believe that the combination of these two immunotherapies increases one's immunity to prostate cancer.
Twelve patients were enrolled in this study. All were given the same doses of GVAX (a 500 million cell first dose followed by bi-weekly 300 million-cell doses for 24 weeks), and, in groups of three, different quantities of ipilimumab administered every four weeks (.3mg, 1mg, 3mg, or 5 mg).
Anti-tumor activity was seen in five of the six patients who received the two highest doses of ipilimumab, including PSA-level declines of greater than 50 percent; these PSA declines were maintained in four of these patients for at least six months, and up to 16 months. Among the patients with PSA-level declines, researchers noted complete resolution of multiple lesions on bone scans in two patients, resolution of cancer spread to abdominal lymph nodes in one patient, and improvement in bone pain in one patient.
The ongoing phase I trial of this combination has enrolled an additional 16 patients with hormone-resistant prostate cancer into an expansion cohort.
Evidence of Efficacy of Antibody Directed Enzyme Prodrug Therapy (ADEPT) in a Phase I Trial in Patients with Advanced Carcinoma
A two-step drug therapy that selectively targets tumors may hold promise for some patients with advanced cancers, according to results of a clinical trial directed by researchers in London.
Scientists at the University College London's Cancer Institute and the Royal Free Hospital used a technique called antibody-directed enzyme prodrug therapy (ADEPT) in 43 patients with previously treated, advanced colorectal, gastro-esophageal, breast, gallbladder, peritoneal, appendix, or pancreatic cancers, or cancers of unknown primary site. The patients received one, two or three ADEPT treatments over a period of two to 10 days, at dosages ranging from 37 mg/m2 to 3,226 mg/m2.
"We found clinically significant responses in 44 percent of patients," said senior author Richard H. Begent, M.D., professor of oncology at the University College London's Cancer Institute. "These results support the case for conducting a randomized phase II clinical trial."
ADEPT is a two-step treatment for cancer that uses an antibody to carry an enzyme directly to the cancer cells. First, an antibody is given with an enzyme attached. Next, a prodrug (inactive anti-cancer drug) is administered. When the prodrug comes in contact with the enzyme, the resulting chemical reaction activates the anti-cancer drug, which is then able to destroy cancer cells while sparing nearby healthy tissue.
In this trial, the researchers gave patients an intravenous dose of MFECP1, a recombinant fusion protein consisting of a fragment of an antibody raised against the substance carcinoembryonic antigen (CEA), which is produced by the cancer, and carboxypeptidase
G2 (CPG2), an enzyme that activates a prodrug. Then, researchers gave patients an intravenous bis-iodo phenol mustard prodrug which is activated by the enzyme within the cancer.
Anti-enzyme antibody developed in 40 percent of patients having a single treatment, 75 percent of patients after two treatments and 100 percent of patients after three treatments.
In addition, imaging scans showed that four of nine patients had partial response, meaning their tumors shrank, at a total prodrug dosage of at least 900 mg/m2. This response was confirmed by a 25 percent reduction in blood levels of CA 19-9, a tumor marker, in three patients who had raised levels before treatment. Stable disease, as defined by RECIST criteria, was seen in 69 percent of patients who had a total prodrug dose of at least 900 mg/m2.
The most common side effects were thrombocytopenia (low platelet count) and neutropenia (low white blood cell count). Side effects were deemed tolerable.
The first use of a live listeria cancer vaccine in man
Phase I/II trial results have shown that the live Listeria cancer vaccine, Lovaxin C, is safe for humans. In addition, three women in the cervical cancer trial had approximately 20 percent tumor reductions, researchers report.
"We are using Listeria to deliver tumor-specific antigens to the immune system in a manner that results in maximal immune and tumor-clearing response," said John Rothman, Ph.D., vice president of clinical development at Advaxis, which is developing Lovaxin C.
The trial included 15 women with progressive, recurrent or advanced cervical cancer. All patients had failed chemotherapy, radiotherapy or surgery. The women had metastatic disease and most were stage IVb.
Listeria monocytogenes infects antigen presenting cells (APCs) -- "a very special piece of immune real estate," Rothman said. These cells consume foreign invaders and instruct the immune system to attack them. Listeria thrives within APCs and thus directs an immune response.
"We bioengineer Listeria both to attenuate it and to cause it to secrete a tumor-specific antigen fused to a listerial protein, which makes it more effective than Listeria that just secretes the tumor antigen," Rothman said. "By doing this we focus a very strong immune attack against the antigen in question, which is typically specific to a tumor."
"What we're doing is taking a lot of evolution that enabled Listeria to infect human immune systems, and an equal amount of evolution that enables humans to get rid of Listeria once this occurs. We are then co-opting and redirecting all of these complex immune responses and targeting them against cancer," Rothman said.
The researchers divided the patients into three groups of five; each group received two doses of either 1x109, 3.3x109 or 1x1010 units of Listeria at three-week intervals. They administered ampicillin five days after each dose, first intravenously and then orally for 10 days.
Each patient developed flu-like symptoms, including fever, chills and nausea with or without vomiting. In the lower doses, these symptoms were treated with non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) and anti-emetics. Patients in the highest dose group had the same but more severe symptoms.
Rothman used the RECIST criteria to assess the tumors in 13 patients. At the end of the study, five patients had progression of their cancer, seven were stable, and one patient showed a partial response to the therapy. Three of the seven stable patients had tumor reductions of about 20 percent.
The partial response patient -- who was stage IVb at trial initiation -- was given six chemotherapy courses and a radical hysterectomy. Currently, she is tumor- free and her blood tests are normal. Six of the 13 patients are surviving, with a median survival of 424 days. Median survival for all 15 treated patients is 327 days.
CTLA-4 blockade for hormone refractory prostate cancer: dose-dependent induction of CD8+ T cell activation and clinical responses
Blocking CTLA-4, a cellular molecule on lymphocytes that inhibits immune response, produced meaningful clinical benefits in patients with prostate cancer that hadn't responded to hormone therapy, according to researchers.
"CTLA-4 blockade works by removing the brakes on the immune system. Our results show that enhancing immune responses in prostate cancer patients can lead to clinical responses," said Lawrence Fong, M.D., a hematology/oncology researcher at University of California, San Francisco.
In a phase 1 trial in 24 patients with metastatic prostate cancer that was unresponsive to hormone therapy, Fong and colleagues treated groups of three to six patients with increasing intravenous doses of ipilimumab (0.5, 1.5 or 3 mg/kg), a fully human anti-CTLA-4 antibody, on the first day of each 28-day treatment cycle. There were four cycles in the trial. The researchers also gave the patients 250 mg/m2/d of granulocyte-macrophage colony-stimulating factor every day for the first two weeks of each cycle.
Researchers monitored T cell activation and toxicity. They performed prostate-specific antigen (PSA) and radiographic tests at enrollment and throughout treatment to assess clinical response.
Three of the six patients treated with the highest ipilimumab dose (3.0 mg/kg x 4) had confirmed declines in PSA levels of more than 50 percent. One of these patients had a partial response in cancer that had spread to the liver.
The researchers found that activation of lymphocytes occurred primarily in the higher doses. They also could detect lymphocytes targeting proteins expressed by prostate cancer cells in some patients following treatment.
Immune-related side effects -- including skin rash, diarrhea and a deficiency in pituitary hormone production -- were most common in the group receiving the higher ipilimumab doses.
Fong and colleagues will continue to study CTLA-4 blockade. "We are studying higher doses of anti-CTLA-4 antibody and look forward to beginning a larger phase 2 trial in the next three to six months," Fong said.
Dendritic and T cell functions in patients with metastatic hormone-refractory prostate cancer treated with GVAX immunotherapy for prostate cancer and ipilumumab
Researchers have found a promising synergy of two therapies to treat metastatic prostate cancer that is resistant to hormone therapy. In a phase I trial, they observed that a combination of GVAX immunotherapy with ipilimumab lowered prostate-specific antigen (PSA) levels in some patients.
"Higher doses of ipilimumab combined with the GVAX vaccine is showing a lot of success in increasing anti-tumor activity in these patients," said Saskia J.A.M. Santegoets, Ph.D., a researcher in the Department of Pathology and Division of Immunotherapy at the Vrije Universiteit Medical Center in the Netherlands. "We're encouraged by the results of this phase I trial and expect ongoing analyses to yield more valuable data about the GVAX/ ipilimumab combination."
In this trial, the vaccine was administered with escalating doses of anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab. Researchers believe that the combination of these two immunotherapies increases one's immunity to prostate cancer.
Twelve patients were enrolled in this study. All were given the same doses of GVAX (a 500 million cell first dose followed by bi-weekly 300 million-cell doses for 24 weeks), and, in groups of three, different quantities of ipilimumab administered every four weeks (.3mg, 1mg, 3mg, or 5 mg).
Anti-tumor activity was seen in five of the six patients who received the two highest doses of ipilimumab, including PSA-level declines of greater than 50 percent; these PSA declines were maintained in four of these patients for at least six months, and up to 16 months. Among the patients with PSA-level declines, researchers noted complete resolution of multiple lesions on bone scans in two patients, resolution of cancer spread to abdominal lymph nodes in one patient, and improvement in bone pain in one patient.
The ongoing phase I trial of this combination has enrolled an additional 16 patients with hormone-resistant prostate cancer into an expansion cohort.
Evidence of Efficacy of Antibody Directed Enzyme Prodrug Therapy (ADEPT) in a Phase I Trial in Patients with Advanced Carcinoma
A two-step drug therapy that selectively targets tumors may hold promise for some patients with advanced cancers, according to results of a clinical trial directed by researchers in London.
Scientists at the University College London's Cancer Institute and the Royal Free Hospital used a technique called antibody-directed enzyme prodrug therapy (ADEPT) in 43 patients with previously treated, advanced colorectal, gastro-esophageal, breast, gallbladder, peritoneal, appendix, or pancreatic cancers, or cancers of unknown primary site. The patients received one, two or three ADEPT treatments over a period of two to 10 days, at dosages ranging from 37 mg/m2 to 3,226 mg/m2.
"We found clinically significant responses in 44 percent of patients," said senior author Richard H. Begent, M.D., professor of oncology at the University College London's Cancer Institute. "These results support the case for conducting a randomized phase II clinical trial."
ADEPT is a two-step treatment for cancer that uses an antibody to carry an enzyme directly to the cancer cells. First, an antibody is given with an enzyme attached. Next, a prodrug (inactive anti-cancer drug) is administered. When the prodrug comes in contact with the enzyme, the resulting chemical reaction activates the anti-cancer drug, which is then able to destroy cancer cells while sparing nearby healthy tissue.
In this trial, the researchers gave patients an intravenous dose of MFECP1, a recombinant fusion protein consisting of a fragment of an antibody raised against the substance carcinoembryonic antigen (CEA), which is produced by the cancer, and carboxypeptidase
G2 (CPG2), an enzyme that activates a prodrug. Then, researchers gave patients an intravenous bis-iodo phenol mustard prodrug which is activated by the enzyme within the cancer.
Anti-enzyme antibody developed in 40 percent of patients having a single treatment, 75 percent of patients after two treatments and 100 percent of patients after three treatments.
In addition, imaging scans showed that four of nine patients had partial response, meaning their tumors shrank, at a total prodrug dosage of at least 900 mg/m2. This response was confirmed by a 25 percent reduction in blood levels of CA 19-9, a tumor marker, in three patients who had raised levels before treatment. Stable disease, as defined by RECIST criteria, was seen in 69 percent of patients who had a total prodrug dose of at least 900 mg/m2.
The most common side effects were thrombocytopenia (low platelet count) and neutropenia (low white blood cell count). Side effects were deemed tolerable.
Teenage Girls Aren't The Only Ones Who Tan Indoors, Older Adults Do So As Well
Think you won't run into grandparents at your local tanning salon? According to new research, you just might. In fact, a recent health survey of American adults suggests that while 20 percent of 18-39 year olds visited tanning beds, as many as 10 percent of those between 50 and 64 years of age and eight percent of those older than 65 tanned indoors.
Researchers at Fox Chase Cancer Center in Philadelphia analyzed data about indoor tanning behaviors collected in 2005 as part of an annual health survey called the National Health Interview Survey (NHIS). Their findings were published online today in the Journal of the American Academy of Dermatology.
"Our results are concerning, especially given the increasing rates of skin cancer, including the deadliest form--melanoma," said Carolyn J. Heckman, Ph.D., a behavioral researcher at Fox Chase. "Ninety percent of all skin cancers are thought to be associated with ultraviolet radiation, which is emitted during indoor tanning. There is a myth that indoor tanning is safer than sunbathing, but this is not the case."
The 2005 in-home interview of 29,394 adults as part of the NHIS survey included questions about indoor tanning in the previous year. Self-reported indoor tanning declined with increasing age from a high of 20 percent among 18-29 year olds to 8 percent among those 65 years of age and older (17 percent among 30- to 39-year-olds, 14 percent among those aged 40 to 49, 10 percent among those 50 to 64). More of those reporting indoor tanning were females, though the division by gender was not as great among older adults (age 18-29, 13 percent male and 27 percent female vs. age 65+, 8 percent male and 7 percent female).
"We conducted these analyses because we know little about the prevalence and correlates of indoor tanning among adults," said Heckman. "Most prior studies have targeted adolescents and young adults. This is the largest study to date investigating indoor tanning in a cohort extending throughout adulthood and we were surprised by how many older adults visit tanning facilities. This is further evidence of the expanding popularity of indoor tanning despite the increased risks for skin cancer."
Skin cancer is the most common form of cancer in the U.S., accounting for half of all human malignancies. The incidence of skin cancer has been increasing annually for the past four decades, and the incidence of malignant melanoma is increasing faster than any other cancer. Skin cancer can be costly and devastating for both health and appearance.
"While the skin cancer susceptibility of older adults is rooted in the sun exposure of their earlier years, indoor tanning contributes to an individual's cumulative exposure and increases their skin cancer risk," added Stuart Lessin, M.D., director of dermatology and the Melanoma Family Risk Assessment Program at Fox Chase.
Other findings from the survey included:
The most important factors associated with higher indoor tanning rates among those under 50 years of age were being female, Caucasian, and having a higher education level.
Adults under 50 who tanned indoors were also more likely to report a moderate to high tanning ability, more past year sunburns, and not staying in the shade when outside.
Factors found to be independently associated with indoor tanning among those 50 and older were having a greater number of sunburns in the past year and not wearing long pants when outside.
"We hope our findings will help inform the public and health professionals who may think indoor tanning isn't a concern for adults," concluded Heckman. "We would also like to see more research conducted in this important area."
This research was supported by grants from the National Cancer Institute.
Researchers at Fox Chase Cancer Center in Philadelphia analyzed data about indoor tanning behaviors collected in 2005 as part of an annual health survey called the National Health Interview Survey (NHIS). Their findings were published online today in the Journal of the American Academy of Dermatology.
"Our results are concerning, especially given the increasing rates of skin cancer, including the deadliest form--melanoma," said Carolyn J. Heckman, Ph.D., a behavioral researcher at Fox Chase. "Ninety percent of all skin cancers are thought to be associated with ultraviolet radiation, which is emitted during indoor tanning. There is a myth that indoor tanning is safer than sunbathing, but this is not the case."
The 2005 in-home interview of 29,394 adults as part of the NHIS survey included questions about indoor tanning in the previous year. Self-reported indoor tanning declined with increasing age from a high of 20 percent among 18-29 year olds to 8 percent among those 65 years of age and older (17 percent among 30- to 39-year-olds, 14 percent among those aged 40 to 49, 10 percent among those 50 to 64). More of those reporting indoor tanning were females, though the division by gender was not as great among older adults (age 18-29, 13 percent male and 27 percent female vs. age 65+, 8 percent male and 7 percent female).
"We conducted these analyses because we know little about the prevalence and correlates of indoor tanning among adults," said Heckman. "Most prior studies have targeted adolescents and young adults. This is the largest study to date investigating indoor tanning in a cohort extending throughout adulthood and we were surprised by how many older adults visit tanning facilities. This is further evidence of the expanding popularity of indoor tanning despite the increased risks for skin cancer."
Skin cancer is the most common form of cancer in the U.S., accounting for half of all human malignancies. The incidence of skin cancer has been increasing annually for the past four decades, and the incidence of malignant melanoma is increasing faster than any other cancer. Skin cancer can be costly and devastating for both health and appearance.
"While the skin cancer susceptibility of older adults is rooted in the sun exposure of their earlier years, indoor tanning contributes to an individual's cumulative exposure and increases their skin cancer risk," added Stuart Lessin, M.D., director of dermatology and the Melanoma Family Risk Assessment Program at Fox Chase.
Other findings from the survey included:
The most important factors associated with higher indoor tanning rates among those under 50 years of age were being female, Caucasian, and having a higher education level.
Adults under 50 who tanned indoors were also more likely to report a moderate to high tanning ability, more past year sunburns, and not staying in the shade when outside.
Factors found to be independently associated with indoor tanning among those 50 and older were having a greater number of sunburns in the past year and not wearing long pants when outside.
"We hope our findings will help inform the public and health professionals who may think indoor tanning isn't a concern for adults," concluded Heckman. "We would also like to see more research conducted in this important area."
This research was supported by grants from the National Cancer Institute.
Cancer Stem Cells Created With New Technique
With a bit of genetic trickery, researchers at the Stanford University School of Medicine have turned normal skin cells into cancer stem cells, a step that will make these naturally rare cells easier to study.
Cancer stem cells are thought to be the ones that drive a cancer, and are therefore the targets of any cancer therapy that must kill them in order to be effective. Understanding these cells has been a challenge, however, because they are rare, difficult to isolate and don't grow well in the lab.
Howard Chang, MD, PhD, assistant professor of dermatology and senior author of the work, said being able to generate cancer stem cells from normal cells will help move that research forward. "The upshot is that there may be a way to directly create cancer stem cells in the lab so you don't always have to purify these rare cells from patients in order to study them directly," he said.
The study also demonstrated that cancer stem cells are much more similar to the stem cells found in embryos, which can develop to form all tissue types, than they are to the more-restricted adult stem cells. This finding has important implications for understanding how cells go awry when they become cancerous.
Cancer stem cells were first discovered in 1994 by researchers at the University of Toronto. In 2003, Michael Clarke, PhD, who was then at the University of Michigan, discovered cancer stem cells in the first solid tumor, breast cancer in this case, showing that the concept of cancer stem cells wasn't restricted to blood cancers. Clarke has since moved to Stanford, where he is the Karel H. and Avice N. Beekhuis Professor in Cancer Biology, and Stanford has become a leader in cancer stem cell research, with teams finding cancer stem cells in head and neck cancer, colorectal cancer and additional blood cancers. Laboratory researchers at the medical school are also beginning to work with clinical groups to apply cancer stem cell findings to patient care.
One question among cancer stem cell researchers has been how those cells originate. "By the time a patient comes to a hospital, they already have a cancer, so that process has already happened," Chang said. Generating cancer stem cells in the lab gives scientists insight into how the transformation happens and could lead to new ways of either stopping the transformation early on or detecting and destroying those cells once they form.
Chang and first author David Wong, MD, PhD, postdoctoral scholar, began to answer the question of how cancer stem cells originate by comparing genetic activity in embryonic stem cells with the activity in normal adult stem cells. They found a large group of genes that were active only in embryonic cells. They then looked at which genes were active in cancer stem cells and found that the pattern resembled that of embryonic stem cells.
The finding was a surprise, given that once embryonic stem cells become committed to forming adult cells, such as skin, brain or blood, they were thought to forever deactivate those embryonic genes. Instead, Chang said this work suggests that when those adult cells become cancerous, they turn those embryonic genes back on.
The group also noticed that the genes active in both embryonic and cancer stem cells are controlled by a few biological master regulators. One of those genes, called Myc, has also been shown recently to help convert normal skin cells into embryonic-like cells.
By activating two genes in addition to Myc in normal skin cells, those cells were transformed into what appeared to be cancer stem cells. When transplanted into laboratory mice, the cells formed tumors, one hallmark of a true cancer stem cell.
From here, Chang and Wong hope to learn more about how these genes activate a cancerous state. "Our particular interest is in using this approach to find the mechanism that turns a normal cell into a cancer stem cell," said Chang, who is also the Kenneth G. and Elaine A. Langone Scholar of the Damon Runyon Cancer Research Foundation.
The work will be published in the April 10 issue of Cell Stem Cell. Other Stanford researchers who contributed to this work include medical student Helen Liu; Todd Ridky, MD, PhD, instructor in dermatology; and David Cassarino, MD, assistant professor of pathology.
The work was funded by grants from the National Institutes or Health, the American Cancer Society and a Dermatology Foundation Research Career Development Award to David Wong.
Cancer stem cells are thought to be the ones that drive a cancer, and are therefore the targets of any cancer therapy that must kill them in order to be effective. Understanding these cells has been a challenge, however, because they are rare, difficult to isolate and don't grow well in the lab.
Howard Chang, MD, PhD, assistant professor of dermatology and senior author of the work, said being able to generate cancer stem cells from normal cells will help move that research forward. "The upshot is that there may be a way to directly create cancer stem cells in the lab so you don't always have to purify these rare cells from patients in order to study them directly," he said.
The study also demonstrated that cancer stem cells are much more similar to the stem cells found in embryos, which can develop to form all tissue types, than they are to the more-restricted adult stem cells. This finding has important implications for understanding how cells go awry when they become cancerous.
Cancer stem cells were first discovered in 1994 by researchers at the University of Toronto. In 2003, Michael Clarke, PhD, who was then at the University of Michigan, discovered cancer stem cells in the first solid tumor, breast cancer in this case, showing that the concept of cancer stem cells wasn't restricted to blood cancers. Clarke has since moved to Stanford, where he is the Karel H. and Avice N. Beekhuis Professor in Cancer Biology, and Stanford has become a leader in cancer stem cell research, with teams finding cancer stem cells in head and neck cancer, colorectal cancer and additional blood cancers. Laboratory researchers at the medical school are also beginning to work with clinical groups to apply cancer stem cell findings to patient care.
One question among cancer stem cell researchers has been how those cells originate. "By the time a patient comes to a hospital, they already have a cancer, so that process has already happened," Chang said. Generating cancer stem cells in the lab gives scientists insight into how the transformation happens and could lead to new ways of either stopping the transformation early on or detecting and destroying those cells once they form.
Chang and first author David Wong, MD, PhD, postdoctoral scholar, began to answer the question of how cancer stem cells originate by comparing genetic activity in embryonic stem cells with the activity in normal adult stem cells. They found a large group of genes that were active only in embryonic cells. They then looked at which genes were active in cancer stem cells and found that the pattern resembled that of embryonic stem cells.
The finding was a surprise, given that once embryonic stem cells become committed to forming adult cells, such as skin, brain or blood, they were thought to forever deactivate those embryonic genes. Instead, Chang said this work suggests that when those adult cells become cancerous, they turn those embryonic genes back on.
The group also noticed that the genes active in both embryonic and cancer stem cells are controlled by a few biological master regulators. One of those genes, called Myc, has also been shown recently to help convert normal skin cells into embryonic-like cells.
By activating two genes in addition to Myc in normal skin cells, those cells were transformed into what appeared to be cancer stem cells. When transplanted into laboratory mice, the cells formed tumors, one hallmark of a true cancer stem cell.
From here, Chang and Wong hope to learn more about how these genes activate a cancerous state. "Our particular interest is in using this approach to find the mechanism that turns a normal cell into a cancer stem cell," said Chang, who is also the Kenneth G. and Elaine A. Langone Scholar of the Damon Runyon Cancer Research Foundation.
The work will be published in the April 10 issue of Cell Stem Cell. Other Stanford researchers who contributed to this work include medical student Helen Liu; Todd Ridky, MD, PhD, instructor in dermatology; and David Cassarino, MD, assistant professor of pathology.
The work was funded by grants from the National Institutes or Health, the American Cancer Society and a Dermatology Foundation Research Career Development Award to David Wong.
Older Australians At Risk Of Sun-related Skin Cancer Death
A new Western Australian study has revealed the mortality from non-melanoma skin cancer (NMSC), commonly considered less dangerous than melanoma, is affecting older Australians at a worrying rate.
Researchers at the Western Australian Institute for Medical Research (WAIMR) found West Australians above the age of 69, especially men, accounted for 70 percent of deaths from non-melanoma skin cancer in WA, and most primary cancers occured in areas of high sun exposure.
The study has prompted health experts to urge older people to stay vigilant about sun protection and get regular skin checks.
The Cancer Council WA Director of Education and Research and co-author of the paper, Terry Slevin, said the study's results should act as a strong reminder for older West Australians to check their skin and see their doctor at the first sign of anything suspicious.
"Older people may have become blasé about NMSC because for the most part they can just be cut out, but as this research shows, NMSC is serious and can be deadly if left untreated," he said.
"It's important people understand that NMSCs are preventable from middle age -- it's wrong to think all the damage to our skin is done in childhood and nothing can be done after that to avoid skin cancer."
The research published in the most recent edition of Cancer Causes Control, found 70 percent of deaths from NMSC occurred among people aged 70 years and over. More than 70 per cent of those were men, and in most cases the primary cancer developed on the face, ears, hands or scalp.
"These results should be a stark reminder for older people, especially blokes, that they should be more vigilant in having their skin checked and do something if they notice any changes in their skin," Mr Slevin said.
"The message these findings send us is that it's never too late to prevent skin cancer and regular skin checks are important to catch skin cancers early, before they become a problem."
Each year in Western Australia, it's estimated that around 30,000 non-melanoma skin cancers are removed and there are 37 deaths from these types of cancers.
Author of the paper, WAIMR Associate Professor Lin Fritschi, said the research was the first definitive evidence that deaths from NMSC in Australia was primarily caused by cancer resulting from excessive sun exposure.
"The average age of death caused by NMSC was about 77 years old, and most primary cancers appeared in areas of high sun exposure -- for men, the scalp was the primary cancer site in a quarter of these deadly cancer cases," she said.
"These cancers can mostly be prevented by applying the 'slip, slop, slap' rule and early detection.
"There could be a number of reasons why older people are not picking up these cancers early enough such as poor eyesight and less mobility to check their own skin, illness or dementia.
"In light of these findings, skin cancer examinations really need to become a high priority for older people as well as their GPs, nurses and carers."
The research found no deaths recorded from basal cell carcinoma (BCC), one of the most common NMSCs, or solar keratosis. Most deaths were associated with squamous cell carcinoma and Merkel cell carcinoma.
Researchers at the Western Australian Institute for Medical Research (WAIMR) found West Australians above the age of 69, especially men, accounted for 70 percent of deaths from non-melanoma skin cancer in WA, and most primary cancers occured in areas of high sun exposure.
The study has prompted health experts to urge older people to stay vigilant about sun protection and get regular skin checks.
The Cancer Council WA Director of Education and Research and co-author of the paper, Terry Slevin, said the study's results should act as a strong reminder for older West Australians to check their skin and see their doctor at the first sign of anything suspicious.
"Older people may have become blasé about NMSC because for the most part they can just be cut out, but as this research shows, NMSC is serious and can be deadly if left untreated," he said.
"It's important people understand that NMSCs are preventable from middle age -- it's wrong to think all the damage to our skin is done in childhood and nothing can be done after that to avoid skin cancer."
The research published in the most recent edition of Cancer Causes Control, found 70 percent of deaths from NMSC occurred among people aged 70 years and over. More than 70 per cent of those were men, and in most cases the primary cancer developed on the face, ears, hands or scalp.
"These results should be a stark reminder for older people, especially blokes, that they should be more vigilant in having their skin checked and do something if they notice any changes in their skin," Mr Slevin said.
"The message these findings send us is that it's never too late to prevent skin cancer and regular skin checks are important to catch skin cancers early, before they become a problem."
Each year in Western Australia, it's estimated that around 30,000 non-melanoma skin cancers are removed and there are 37 deaths from these types of cancers.
Author of the paper, WAIMR Associate Professor Lin Fritschi, said the research was the first definitive evidence that deaths from NMSC in Australia was primarily caused by cancer resulting from excessive sun exposure.
"The average age of death caused by NMSC was about 77 years old, and most primary cancers appeared in areas of high sun exposure -- for men, the scalp was the primary cancer site in a quarter of these deadly cancer cases," she said.
"These cancers can mostly be prevented by applying the 'slip, slop, slap' rule and early detection.
"There could be a number of reasons why older people are not picking up these cancers early enough such as poor eyesight and less mobility to check their own skin, illness or dementia.
"In light of these findings, skin cancer examinations really need to become a high priority for older people as well as their GPs, nurses and carers."
The research found no deaths recorded from basal cell carcinoma (BCC), one of the most common NMSCs, or solar keratosis. Most deaths were associated with squamous cell carcinoma and Merkel cell carcinoma.
Ovarian Cancer Stem Cells Identified, Characterized
Researchers at Yale School of Medicine have identified, characterized and cloned ovarian cancer stem cells and have shown that these stem cells may be the source of ovarian cancer's recurrence and its resistance to chemotherapy.
"These results bring us closer to more effective and targeted treatment for epithelial ovarian cancer, one of the most lethal forms of cancer," said Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.
Mor presented his findings recently at the annual meeting of the American Association for Cancer Research (AACR) Meeting in San Diego, California.
Cancerous tumors are made up of cells that are both cancerous and non-cancerous. Within cancerous cells, there is a further subclass referred to as cancer stem cells, which can replicate indefinitely.
"Present chemotherapy modalities eliminate the bulk of the tumor cells, but cannot eliminate a core of these cancer stem cells that have a high capacity for renewal," said Mor, who is also a member of the Yale Cancer Center. "Identification of these cells, as we have done here, is the first step in the development of therapeutic modalities."
Mor and colleagues isolated cells from 80 human samples of either peritoneal fluid or solid tumors. The cancer stem cells that were identified were positive for traditional cancer stem cell markers including CD44 and MyD88. These cells also showed a high capacity for repair and self-renewal.
The isolated cells formed tumors 100 percent of the time. Within those tumors, 10 percent of the cells were positive for cancer stem cell marker CD44, while 90 percent were CD44 negative.
Mor and his team were able to isolate and clone the ovarian cancer stem cells. They found that these cells were highly resistant to conventional chemotherapy while the non-cancer stem cells responded to treatment. "Isolating and cloning these cells will lead to development of new treatments to target and eliminate the cancer stem cells and hopefully prevent recurrence," said Mor.
"These results bring us closer to more effective and targeted treatment for epithelial ovarian cancer, one of the most lethal forms of cancer," said Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.
Mor presented his findings recently at the annual meeting of the American Association for Cancer Research (AACR) Meeting in San Diego, California.
Cancerous tumors are made up of cells that are both cancerous and non-cancerous. Within cancerous cells, there is a further subclass referred to as cancer stem cells, which can replicate indefinitely.
"Present chemotherapy modalities eliminate the bulk of the tumor cells, but cannot eliminate a core of these cancer stem cells that have a high capacity for renewal," said Mor, who is also a member of the Yale Cancer Center. "Identification of these cells, as we have done here, is the first step in the development of therapeutic modalities."
Mor and colleagues isolated cells from 80 human samples of either peritoneal fluid or solid tumors. The cancer stem cells that were identified were positive for traditional cancer stem cell markers including CD44 and MyD88. These cells also showed a high capacity for repair and self-renewal.
The isolated cells formed tumors 100 percent of the time. Within those tumors, 10 percent of the cells were positive for cancer stem cell marker CD44, while 90 percent were CD44 negative.
Mor and his team were able to isolate and clone the ovarian cancer stem cells. They found that these cells were highly resistant to conventional chemotherapy while the non-cancer stem cells responded to treatment. "Isolating and cloning these cells will lead to development of new treatments to target and eliminate the cancer stem cells and hopefully prevent recurrence," said Mor.
Interleukin-12 Indicates Survival Prospects For Melanoma Patients
Higher blood levels of an immune system protein predict poor survival prospects for melanoma patients with advanced disease, researchers at The University of Texas M. D. Anderson Cancer Center reported recently at the annual meeting of the American Association for Cancer Research.
Their finding that elevated levels of interleukin-12 (IL-12) are a marker of poor prognosis also points to a molecular explanation for a long-known risk factor for melanoma patients - older age.
Among 150 patients with Stage III melanoma, the study found that the highest levels of IL-12 are associated with a nearly 5-fold risk of death. Although older stage III patients also had an elevated risk of death, age was not a prognostic factor independent of IL-12.
"Melanoma in some cases can be vulnerable to attack by a patient's immune system," said senior researcher Jeffrey Lee, M. D., professor in M. D. Anderson's Department of Surgical Oncology. "What we've found could be evidence of a dysfunctional immune response that actually fuels the growth of melanoma."
Blood-born IL-12 provides both an accessible prognostic marker and a key connection to other signaling proteins; IL-12 as well as these related proteins already have been targeted by antibody therapies in certain autoimmune disorders, Lee said.
The research team examined age, stage of disease, and IL-12 levels in 658 melanoma patients - 445 with stage I or II disease, 150 with stage 3 and 63 at stage IV.
"First, we found that IL-12 levels increase with age," says first author and study presenter Yun Shin Chun, M.D. The mean levels of the protein increased at every age level above age 40. (See Chart)
Age, disease stage and IL-12 levels were then analyzed separately as prognostic factors. Increases in all three were associated with poor overall survival.
"When we analyzed these three factors together, only stage of disease and IL-12 levels were independent predictors of overall survival," Chun said. Age dropped completely out of the picture. Stage of disease was the most powerful prognostic factor.
Both IL-12 and IL-23 are cytokines, proteins that tell cells and other proteins what to do. Cytokines like IL-12 and IL-23 are particularly vital to immune system function. The general level of a person's immune function declines with age, Lee said, as do the levels of most cytokines. The rise of IL-12p40 with age is a relative anomaly.
Chun, Lee and colleagues are investigating IL-12's connection to the tumor promoting IL-23 and about 30 other cytokines in high-risk melanoma patients. Some of the suspect cytokines, including IL-12 and IL-23, already are targeted by therapies used autoimmune disease, Lee noted.
Funding for the research was provided by The Marit Peterson Fund for Melanoma Research, and the M.D. Anderson's SPORE grant in melanoma from the National Cancer Institute.
Co-authors with Chun and Lee are Yuling Wang, Amy Vo, Huey Liu, Daniel Wang, Jeffrey Gershenwald, Janice Cormier, Merrick Ross, Christopher Schacherer and Dana McClain, all of M. D. Anderson's Department of Surgical Oncology; and John Reveille, of the Department of Internal Medicine, division of Rheumatology, University of Texas Health Science Center at Houston.
Their finding that elevated levels of interleukin-12 (IL-12) are a marker of poor prognosis also points to a molecular explanation for a long-known risk factor for melanoma patients - older age.
Among 150 patients with Stage III melanoma, the study found that the highest levels of IL-12 are associated with a nearly 5-fold risk of death. Although older stage III patients also had an elevated risk of death, age was not a prognostic factor independent of IL-12.
"Melanoma in some cases can be vulnerable to attack by a patient's immune system," said senior researcher Jeffrey Lee, M. D., professor in M. D. Anderson's Department of Surgical Oncology. "What we've found could be evidence of a dysfunctional immune response that actually fuels the growth of melanoma."
Blood-born IL-12 provides both an accessible prognostic marker and a key connection to other signaling proteins; IL-12 as well as these related proteins already have been targeted by antibody therapies in certain autoimmune disorders, Lee said.
The research team examined age, stage of disease, and IL-12 levels in 658 melanoma patients - 445 with stage I or II disease, 150 with stage 3 and 63 at stage IV.
"First, we found that IL-12 levels increase with age," says first author and study presenter Yun Shin Chun, M.D. The mean levels of the protein increased at every age level above age 40. (See Chart)
Age, disease stage and IL-12 levels were then analyzed separately as prognostic factors. Increases in all three were associated with poor overall survival.
"When we analyzed these three factors together, only stage of disease and IL-12 levels were independent predictors of overall survival," Chun said. Age dropped completely out of the picture. Stage of disease was the most powerful prognostic factor.
Both IL-12 and IL-23 are cytokines, proteins that tell cells and other proteins what to do. Cytokines like IL-12 and IL-23 are particularly vital to immune system function. The general level of a person's immune function declines with age, Lee said, as do the levels of most cytokines. The rise of IL-12p40 with age is a relative anomaly.
Chun, Lee and colleagues are investigating IL-12's connection to the tumor promoting IL-23 and about 30 other cytokines in high-risk melanoma patients. Some of the suspect cytokines, including IL-12 and IL-23, already are targeted by therapies used autoimmune disease, Lee noted.
Funding for the research was provided by The Marit Peterson Fund for Melanoma Research, and the M.D. Anderson's SPORE grant in melanoma from the National Cancer Institute.
Co-authors with Chun and Lee are Yuling Wang, Amy Vo, Huey Liu, Daniel Wang, Jeffrey Gershenwald, Janice Cormier, Merrick Ross, Christopher Schacherer and Dana McClain, all of M. D. Anderson's Department of Surgical Oncology; and John Reveille, of the Department of Internal Medicine, division of Rheumatology, University of Texas Health Science Center at Houston.
Most Lethal Melanomas Are On Scalp And Neck
People with scalp or neck melanomas die at nearly twice the rate of people with melanoma elsewhere on the body, including the face or ears, researchers at the University of North Carolina at Chapel Hill have found.
The analysis of 51,704 melanoma cases in the U.S. confirms that survival rates differ depending on where skin cancer first appears. Those with scalp or neck melanomas die at a rate 1.84 times higher than those with melanomas on the extremities, after controlling for the possible influences of age, gender, tumor thickness and ulceration.
"Scalp and neck melanomas patients have a higher rate of death than patients with melanoma anywhere else on the body," said Nancy Thomas, M.D., Ph.D., associate professor of dermatology in the UNC School of Medicine, a member of the UNC Lineberger Comprehensive Cancer Center and the study's senior author. Anne Lachiewicz, a medical student in the UNC School of Medicine, is the lead author of the study.
Thomas recommends that physicians pay special attention to the scalp when examining patients for signs of skin cancer. "Only six percent of melanoma patients present with the disease on the scalp or neck, but those patients account for 10 percent of melanoma deaths. That's why we need to take extra time to look at the scalp during full-skin examinations," she said.
The study helps address a controversy among cancer researchers: whether scalp and neck skin cancer is more lethal primarily because it's diagnosed later than other melanomas. "That was the thinking of a lot of people in the field," Thomas said. But the analysis indicates that the presence of the melanoma on the scalp or neck, in itself, is an indicator of a poorer prognosis.
"We think there's something different about scalp and neck melanomas," Thomas said. "This gives us directions for research to look at tumor cell types in those areas at the molecular level and to see if there are differences. I'm interested in identifying the mutations that drive malignancy."
Thomas, Lachiewicz and their colleagues analyzed data from 13 National Cancer Institute Surveillance Epidemiology and End Results (SEER) Program registries in nine states. Each case represented the first invasive melanoma diagnosed among non-Hispanic white adults between 1992 and 2003.
Patients with scalp or neck melanomas were older (59 years) than patients with other melanomas (55 years), and more likely to be male (74 percent versus 54 percent, respectively). In addition, scalp and neck melanomas were thicker (0.8 millimeters) than melanomas at other sites (0.6 millimeters) and more likely to be ulcerated. Lymph node involvement was also more common in patients with scalp-neck melanomas.
Melanomas on the extremities or on the face or ears had the best prognosis. The five-year melanoma-specific survival rate for patients with scalp or neck melanomas was 83 percent, compared with 92 percent for patients with melanomas at other sites. The ten-year survival rate was 76 percent for scalp or neck melanomas and 89 percent for other melanomas.
Journal reference: Arch Dermatol. 2008;144[4]:515-521.
Study co-authors are Drs. Marianne Berwick and Charles Wiggins of the University of New Mexico.
Funding was provided by the National Cancer Institute and a Holderness Medical Foundation Fellowship to Lachiewicz.
The analysis of 51,704 melanoma cases in the U.S. confirms that survival rates differ depending on where skin cancer first appears. Those with scalp or neck melanomas die at a rate 1.84 times higher than those with melanomas on the extremities, after controlling for the possible influences of age, gender, tumor thickness and ulceration.
"Scalp and neck melanomas patients have a higher rate of death than patients with melanoma anywhere else on the body," said Nancy Thomas, M.D., Ph.D., associate professor of dermatology in the UNC School of Medicine, a member of the UNC Lineberger Comprehensive Cancer Center and the study's senior author. Anne Lachiewicz, a medical student in the UNC School of Medicine, is the lead author of the study.
Thomas recommends that physicians pay special attention to the scalp when examining patients for signs of skin cancer. "Only six percent of melanoma patients present with the disease on the scalp or neck, but those patients account for 10 percent of melanoma deaths. That's why we need to take extra time to look at the scalp during full-skin examinations," she said.
The study helps address a controversy among cancer researchers: whether scalp and neck skin cancer is more lethal primarily because it's diagnosed later than other melanomas. "That was the thinking of a lot of people in the field," Thomas said. But the analysis indicates that the presence of the melanoma on the scalp or neck, in itself, is an indicator of a poorer prognosis.
"We think there's something different about scalp and neck melanomas," Thomas said. "This gives us directions for research to look at tumor cell types in those areas at the molecular level and to see if there are differences. I'm interested in identifying the mutations that drive malignancy."
Thomas, Lachiewicz and their colleagues analyzed data from 13 National Cancer Institute Surveillance Epidemiology and End Results (SEER) Program registries in nine states. Each case represented the first invasive melanoma diagnosed among non-Hispanic white adults between 1992 and 2003.
Patients with scalp or neck melanomas were older (59 years) than patients with other melanomas (55 years), and more likely to be male (74 percent versus 54 percent, respectively). In addition, scalp and neck melanomas were thicker (0.8 millimeters) than melanomas at other sites (0.6 millimeters) and more likely to be ulcerated. Lymph node involvement was also more common in patients with scalp-neck melanomas.
Melanomas on the extremities or on the face or ears had the best prognosis. The five-year melanoma-specific survival rate for patients with scalp or neck melanomas was 83 percent, compared with 92 percent for patients with melanomas at other sites. The ten-year survival rate was 76 percent for scalp or neck melanomas and 89 percent for other melanomas.
Journal reference: Arch Dermatol. 2008;144[4]:515-521.
Study co-authors are Drs. Marianne Berwick and Charles Wiggins of the University of New Mexico.
Funding was provided by the National Cancer Institute and a Holderness Medical Foundation Fellowship to Lachiewicz.
Tuesday, 22 April 2008
Many African-Americans Have A Gene That Prolongs Life After Heart Failure
About 40 percent of African-Americans have a genetic variant that can protect them after heart failure and prolong their lives, according to research conducted at Washington University School of Medicine in St. Louis and collaborating institutions.
The genetic variant has an effect that resembles that of beta blockers, drugs widely prescribed for heart failure. The new study offers a reason why beta blockers don't appear to benefit some African-Americans.
"For several years a controversy has existed in the cardiovascular field because of conflicting reports about whether beta blockers helped African-American patients," says senior author Gerald W. Dorn II, M.D., professor of medicine, associate chairman for translational research and director of the Center for Pharmacogenomics at Washington University.
"By mimicking the effect of beta blockers, the genetic variant makes it appear as if beta blockers aren't effective in these patients," he explains. "But although beta blockers have no additional benefit in heart failure patients with the variant, they are equally effective in Caucasian and African-American patients without the variant."
Co-author Stephen B. Liggett, M.D., professor of medicine and physiology at the University of Maryland School of Medicine and director of its cardiopulmonary genomics program says the discovery adds to the accumulating evidence that genetic differences contribute to the way people respond to medications and should encourage the use of genetic testing in clinical trials to identify people who can benefit from therapy tailored to their genetic makeup.
About 5 million people in the United States have heart failure, and it results in about 300,000 deaths each year. Beta blockers slow heart rate and lower blood pressure to decrease the heart's workload and prevent lethal cardiac arrhythmias.
While Caucasians with heart failure participating in clinical studies of beta blockers have shown clear benefit from the drugs, the evidence for benefit in African-Americans has been ambiguous. The current study, reported online April 20, 2008, in Nature Medicine, identified one particular race-specific gene variant that seems to account mechanistically and biologically for these indeterminate results.
The gene codes for an enzyme called GRK5, which depresses the response to adrenaline and similar hormonal substances that increase how hard the heart works. Adrenaline is a hormone released from the adrenal glands that prompts the "fight-or-flight" response -- it increases cardiac output to give a sudden burst of energy.
In heart failure, decreased blood flow from the struggling heart ramps up the body's secretion of adrenaline to compensate for a lower blood flow. Overproduction of the hormone makes the weakened heart pump harder, but eventually worsens heart failure.
Beta blockers alleviate this problem by blocking adrenaline at its receptor in the heart and blood vessels. GRK enzymes mimic this effect by serving as "speed governors" that work like the governor in an engine to prevent adrenaline from over-revving the heart, says Dorn.
The researchers -- including three equally contributing co-authors: Liggett, Sharon Cresci, M.D., assistant professor of medicine in the Cardiovascular Division at Washington University and a cardiologist at Barnes-Jewish Hospital, and Reagan J. Kelly, Ph.D., at the University of Michigan -- found that 41 percent of African-Americans have a variant GRK5 gene that more effectively suppresses the action of adrenaline than the more common version of the gene. People with the variant gene could be said to have a natural beta blocker, Dorn says. The variant is extremely rare in Caucasians, accounting for its predominant effects in African-Americans.
The researchers showed that African-American heart failure patients with this genetic variant have about the same survival rate even if they don't take beta blockers as Caucasian and African-American heart failure patients who do take beta blockers.
"That doesn't mean African-Americans with heart failure need to be tested for the genetic variant to decide whether to take beta blockers," Dorn says. "Under the supervision of a cardiologist, beta blockers have very low risk but huge benefits, and I am comfortable prescribing them to any heart failure patients who do not have a specific contraindication to the drug."
"This is a step toward individualized therapy," Cresci says. "Medical research is working to identify many genetic variants that someday can ensure that patients receive the medications that are most appropriate for them. Right now, we know one variant that influences beta blocker efficacy, and we are continuing our research into this and other relevant genetic variants."
The human heart has two forms of GRK: GRK2 and GRK5. The researchers meticulously searched the DNA sequence of these genes in 96 people of European-American, African-American or Chinese descent to look for differences. They found most people, no matter their race, had exactly the same DNA sequence in GRK2 or GRK5. But there was one common variation in the DNA sequence, a variation called GRK5-Leu41, the variant that more than 40 percent of African-Americans have.
To determine the effect of the GRK5-Leu41 variant, the team studied the course of progression of heart failure in 375 African-American patients. They looked for survival time or time to heart transplant, comparing people with the variant to those without. Some of these patients were taking beta blockers and some were not.
In patients who did not take beta blockers, the researchers found that those with the variant lived almost twice as long as those with the more common version of the GRK5 gene. Beta blockers prolonged life to the same degree as the protective GRK5 variant, but did not further increase the already improved survival of those with the variant.
"These results offer an explanation for the confusion that has occurred in this area since clinical trials of beta blockers began," Dorn says. "Our study demonstrates a mechanism that should lay to rest the question about whether beta blockers are effective in African-Americans -- they absolutely are in those who don't have this genetic variant."
Other institutions collaborating in the study are the University of Cincinnati, Thomas Jefferson University and the University of Missouri, Kansas City.
Liggett SB, Cresci S, Kelly RJ, Syed FM, Matkovich SJ, Hahn HS, Diwan A, Martini JS, Sparks L, Parekh RR Spertus JA, Koch WJ, Kardia SLR, Dorn II GW. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nature Medicine April 20, 2008 (advance online publishing).
Funding from National Heart, Lung, and Blood Institute supported this research.
The genetic variant has an effect that resembles that of beta blockers, drugs widely prescribed for heart failure. The new study offers a reason why beta blockers don't appear to benefit some African-Americans.
"For several years a controversy has existed in the cardiovascular field because of conflicting reports about whether beta blockers helped African-American patients," says senior author Gerald W. Dorn II, M.D., professor of medicine, associate chairman for translational research and director of the Center for Pharmacogenomics at Washington University.
"By mimicking the effect of beta blockers, the genetic variant makes it appear as if beta blockers aren't effective in these patients," he explains. "But although beta blockers have no additional benefit in heart failure patients with the variant, they are equally effective in Caucasian and African-American patients without the variant."
Co-author Stephen B. Liggett, M.D., professor of medicine and physiology at the University of Maryland School of Medicine and director of its cardiopulmonary genomics program says the discovery adds to the accumulating evidence that genetic differences contribute to the way people respond to medications and should encourage the use of genetic testing in clinical trials to identify people who can benefit from therapy tailored to their genetic makeup.
About 5 million people in the United States have heart failure, and it results in about 300,000 deaths each year. Beta blockers slow heart rate and lower blood pressure to decrease the heart's workload and prevent lethal cardiac arrhythmias.
While Caucasians with heart failure participating in clinical studies of beta blockers have shown clear benefit from the drugs, the evidence for benefit in African-Americans has been ambiguous. The current study, reported online April 20, 2008, in Nature Medicine, identified one particular race-specific gene variant that seems to account mechanistically and biologically for these indeterminate results.
The gene codes for an enzyme called GRK5, which depresses the response to adrenaline and similar hormonal substances that increase how hard the heart works. Adrenaline is a hormone released from the adrenal glands that prompts the "fight-or-flight" response -- it increases cardiac output to give a sudden burst of energy.
In heart failure, decreased blood flow from the struggling heart ramps up the body's secretion of adrenaline to compensate for a lower blood flow. Overproduction of the hormone makes the weakened heart pump harder, but eventually worsens heart failure.
Beta blockers alleviate this problem by blocking adrenaline at its receptor in the heart and blood vessels. GRK enzymes mimic this effect by serving as "speed governors" that work like the governor in an engine to prevent adrenaline from over-revving the heart, says Dorn.
The researchers -- including three equally contributing co-authors: Liggett, Sharon Cresci, M.D., assistant professor of medicine in the Cardiovascular Division at Washington University and a cardiologist at Barnes-Jewish Hospital, and Reagan J. Kelly, Ph.D., at the University of Michigan -- found that 41 percent of African-Americans have a variant GRK5 gene that more effectively suppresses the action of adrenaline than the more common version of the gene. People with the variant gene could be said to have a natural beta blocker, Dorn says. The variant is extremely rare in Caucasians, accounting for its predominant effects in African-Americans.
The researchers showed that African-American heart failure patients with this genetic variant have about the same survival rate even if they don't take beta blockers as Caucasian and African-American heart failure patients who do take beta blockers.
"That doesn't mean African-Americans with heart failure need to be tested for the genetic variant to decide whether to take beta blockers," Dorn says. "Under the supervision of a cardiologist, beta blockers have very low risk but huge benefits, and I am comfortable prescribing them to any heart failure patients who do not have a specific contraindication to the drug."
"This is a step toward individualized therapy," Cresci says. "Medical research is working to identify many genetic variants that someday can ensure that patients receive the medications that are most appropriate for them. Right now, we know one variant that influences beta blocker efficacy, and we are continuing our research into this and other relevant genetic variants."
The human heart has two forms of GRK: GRK2 and GRK5. The researchers meticulously searched the DNA sequence of these genes in 96 people of European-American, African-American or Chinese descent to look for differences. They found most people, no matter their race, had exactly the same DNA sequence in GRK2 or GRK5. But there was one common variation in the DNA sequence, a variation called GRK5-Leu41, the variant that more than 40 percent of African-Americans have.
To determine the effect of the GRK5-Leu41 variant, the team studied the course of progression of heart failure in 375 African-American patients. They looked for survival time or time to heart transplant, comparing people with the variant to those without. Some of these patients were taking beta blockers and some were not.
In patients who did not take beta blockers, the researchers found that those with the variant lived almost twice as long as those with the more common version of the GRK5 gene. Beta blockers prolonged life to the same degree as the protective GRK5 variant, but did not further increase the already improved survival of those with the variant.
"These results offer an explanation for the confusion that has occurred in this area since clinical trials of beta blockers began," Dorn says. "Our study demonstrates a mechanism that should lay to rest the question about whether beta blockers are effective in African-Americans -- they absolutely are in those who don't have this genetic variant."
Other institutions collaborating in the study are the University of Cincinnati, Thomas Jefferson University and the University of Missouri, Kansas City.
Liggett SB, Cresci S, Kelly RJ, Syed FM, Matkovich SJ, Hahn HS, Diwan A, Martini JS, Sparks L, Parekh RR Spertus JA, Koch WJ, Kardia SLR, Dorn II GW. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nature Medicine April 20, 2008 (advance online publishing).
Funding from National Heart, Lung, and Blood Institute supported this research.
Patients Receive Heart Valve Replacements Without Surgery Using High-tech Device
Interventional cardiologists at Rush University Medical Center now offer a minimally-invasive transcatheter valve replacement procedure for patients with congenital heart disease that doesn’t involve open heart surgery.
Rush is one of three sites taking part in the investigational device exemption (IDE) feasibility study of minimally-invasive pulmonic valves and successfully implanted the first three patients enrolled in the trial on April 17.
“We were able to successfully implant the Edwards SAPIEN transcatheter heart valve percutaneously in the first three patients treated in this trial. All of the patients are recovering and are expected to go home today," said Dr. Ziyad M. Hijazi, director of the Rush Center for Congenital and Structural Heart Disease, chief of the section of pediatric cardiology and professor in the departments of pediatrics and internal medicine at Rush University, Chicago. "Patients with congenital right ventricular outflow tract problems typically face the burden of multiple open-heart surgeries throughout their lives, either to replace their 'native' diseased valves or, as they age, their bioprosthetic replacement valves.”
Hijazi, an interventional cardiologist and pioneer in nonsurgical repair of the heart, and his colleagues, Dr. Clifford J. Kavinsky and Dr. Zahid Amin, used a bovine pericardial heart valve that can be compressed onto a balloon to the approximate diameter of a pencil, threaded from the leg into the circulatory system and deployed across the patient’s pulmonary valve. The valve replacement is accomplished as a “beating heart” procedure, without requiring cardiopulmonary bypass or an open-chest incision.
Edwards Lifesciences Corporation of Irvine, Calif., makes the Edwards SAPIEN transcatheter valve that was implanted.
“We can replace heart valves in high-risk patients with severe pulmonary stenosis (abnormal narrowing in a blood vessel) who might not be candidates for conventional valve replacement surgery. Instead, these patients can benefit from a transcatheter valve replacement procedure done minimally-invasively, without cardio-pulmonary bypass, that has the potential to shorten recovery time,” said Hijazi.. "This clinical study will enable physicians to offer a minimally-invasive alternative to symptomatic patients with a regurgitant, or leaky, pulmonary valve conduit, giving them the opportunity to recover and resume their normal activities."
“My team is proud to be able to address this serious unmet patient need and to offer the chance to take one or more surgeries out of the treatment course for these patients,” said Hijazi.
The U.S. Food and Drug Administration (FDA) conditionally approved the investigational device exemption (IDE) clinical trial in late 2007. The study of 30 patients at three hospitals will enable the collection of safety and effectiveness data, ultimately in support of a commercial approval application.
Rush is one of three sites taking part in the investigational device exemption (IDE) feasibility study of minimally-invasive pulmonic valves and successfully implanted the first three patients enrolled in the trial on April 17.
“We were able to successfully implant the Edwards SAPIEN transcatheter heart valve percutaneously in the first three patients treated in this trial. All of the patients are recovering and are expected to go home today," said Dr. Ziyad M. Hijazi, director of the Rush Center for Congenital and Structural Heart Disease, chief of the section of pediatric cardiology and professor in the departments of pediatrics and internal medicine at Rush University, Chicago. "Patients with congenital right ventricular outflow tract problems typically face the burden of multiple open-heart surgeries throughout their lives, either to replace their 'native' diseased valves or, as they age, their bioprosthetic replacement valves.”
Hijazi, an interventional cardiologist and pioneer in nonsurgical repair of the heart, and his colleagues, Dr. Clifford J. Kavinsky and Dr. Zahid Amin, used a bovine pericardial heart valve that can be compressed onto a balloon to the approximate diameter of a pencil, threaded from the leg into the circulatory system and deployed across the patient’s pulmonary valve. The valve replacement is accomplished as a “beating heart” procedure, without requiring cardiopulmonary bypass or an open-chest incision.
Edwards Lifesciences Corporation of Irvine, Calif., makes the Edwards SAPIEN transcatheter valve that was implanted.
“We can replace heart valves in high-risk patients with severe pulmonary stenosis (abnormal narrowing in a blood vessel) who might not be candidates for conventional valve replacement surgery. Instead, these patients can benefit from a transcatheter valve replacement procedure done minimally-invasively, without cardio-pulmonary bypass, that has the potential to shorten recovery time,” said Hijazi.. "This clinical study will enable physicians to offer a minimally-invasive alternative to symptomatic patients with a regurgitant, or leaky, pulmonary valve conduit, giving them the opportunity to recover and resume their normal activities."
“My team is proud to be able to address this serious unmet patient need and to offer the chance to take one or more surgeries out of the treatment course for these patients,” said Hijazi.
The U.S. Food and Drug Administration (FDA) conditionally approved the investigational device exemption (IDE) clinical trial in late 2007. The study of 30 patients at three hospitals will enable the collection of safety and effectiveness data, ultimately in support of a commercial approval application.
Children With ADHD Should Get Heart Tests Before Treatment With Stimulant Drugs
Children with attention deficit hyperactivity disorder (ADHD) should get careful cardiac evaluation and monitoring -- including an electrocardiogram (ECG) -- before treatment with stimulant drugs, a new American Heart Association statement recommends.
The scientific statement on Cardiovascular Monitoring of Children and Adolescents with Heart Disease Receiving Stimulant Drugs is published online in Circulation: Journal of the American Heart Association.
In 1999, concerns over potential cardiovascular effects of psychotropic drugs, especially tricyclic antidepressants, but including stimulants, prompted an American Heart Association Scientific Statement: Cardiovascular Monitoring of Children and Adolescents Receiving Psychotropic Drugs. However, no specific cardiovascular monitoring was recommended for the use of stimulant medications. Warnings from the U. S. Food and Drug Administration (FDA) about stimulant medications and public concern for the safety of using them have prompted the current statement.
Studies have shown that stimulant medications like those used to treat ADHD can increase heart rate and blood pressure. These side effects are insignificant for most children with ADHD; however, they're an important consideration for children who have a heart condition. Certain heart conditions increase the risk for sudden cardiac death (SCD), which occurs when the heart rhythm becomes erratic and doesn't pump blood through the body.
Doctors usually use a physical exam and the patient and family history to detect the risk for or presence of health problems before beginning new treatments, including prescribing medication. But some of the cardiac conditions associated with SCD may not be noticed in a routine physical exam. Many of these conditions are subtle and do not result in symptoms or have symptoms that are vague such as palpitations, fainting or chest pain.
That's why the statement writing group recommends adding an ECG to pre-treatment evaluations for children with ADHD. An ECG measures the heart's electrical activity and can often identify heart rhythm abnormalities such as those that can lead to sudden cardiac death.
"After ADHD is diagnosed, but before therapy with a stimulant or other medication is begun, we suggest that an ECG be added to the pre-treatment evaluation to increase the likelihood of identifying cardiac conditions that may place the child at risk for sudden death," said Victoria L. Vetter, M.D., head of the statement writing committee and Professor of Pediatrics at the University of Pennsylvania School of Medicine in Philadelphia.
Vetter also said doctors should evaluate children and adolescents already taking these medications if they were not evaluated when they started the treatment.
If heart problems are suspected after the evaluation, children should be referred to a pediatric cardiologist. Once stimulant treatment begins, children should have their heart health monitored periodically, with a blood pressure check within one to three months, then again at routine follow-ups every six to 12 months.
"Children can have undiagnosed heart conditions without showing symptoms," Vetter said. "Furthermore, a child's body changes constantly, with some conditions not appearing until adolescence."
If the initial ECG was taken before age 12 years, it may be useful to do a repeat ECG after the child is over age 12 years, the statement says.
Widespread use of ECGs to detect heart abnormalities, including screenings for competitive athletes, is not routinely recommended by the American Heart Association. However, the writing group found using ECG screening in this specific population of children prescribed ADHD medication is medically indicated and reasonably priced. That said, however, lack of an ECG shouldn't mean that kids who need ADHD treatment can't get it.
"While we feel that an ECG is reasonable and helpful as a tool to identify children with cardiac conditions that can lead to SCD, if, in the view of their physician, a child requires immediate treatment with stimulant medications, this recommendation is not meant to keep them from getting that treatment," said Vetter, who added that some children may not have access to a pediatric cardiologist who can evaluate an ECG or perform a cardiology consultation.
In 2003, an estimated 2.5 million children took medication for ADHD. Surveys indicate that ADHD affects an estimated 4 percent to 12 percent of all school-aged children in the United States, and it appears more common in children with heart conditions. Studies report that, depending on the specific cardiac condition, 33 percent to 42 percent of pediatric cardiac patients have ADHD, Vetter said. The number of undiagnosed children with heart conditions is unknown as routine heart screening is not performed, but Vetter said that a recent pilot study she presented at the American Heart Association's 2007 Scientific Session indicated that up to 2 percent of healthy school aged children had potentially serious undiagnosed cardiac conditions identified by an ECG.
Data from the FDA showed that between 1999 and 2004, 19 children taking ADHD medications died suddenly and 26 children experienced cardiovascular events such as strokes, cardiac arrests and heart palpitations. Since February 2007, the FDA has required all manufacturers of drug products approved for ADHD treatment to develop Medication Guidelines to alert patients to possible cardiovascular risks.
Future studies are necessary to assess the true risk of SCD in association with stimulant drugs in children and adolescents with and without heart disease, Vetter said. However, studying SCD associated with drugs is difficult because the government's reporting system is voluntary, which means local data on these types of deaths isn't always reported nationally.
A registry of SCD events is necessary for further investigating this issue, the writing committee said. Such a registry would allow for a more accurate understanding of SCD, including the true incidence of it and the potential effectiveness of universal ECG testing and pre-participation screening questionnaires.
The statement writing committee said its recommendations are not intended to limit the appropriate use of stimulants in children with ADHD.
"Our intention is to provide the physician with some tools to help identify heart conditions in children with ADHD, and help them make decisions about the use of stimulant medications and the follow-up of children who take them," Vetter said. "The goal is to allow treatment of ADHD, while attempting to lower the cardiac risk of these products in susceptible children."
The scientific statement on Cardiovascular Monitoring of Children and Adolescents with Heart Disease Receiving Stimulant Drugs is published online in Circulation: Journal of the American Heart Association.
In 1999, concerns over potential cardiovascular effects of psychotropic drugs, especially tricyclic antidepressants, but including stimulants, prompted an American Heart Association Scientific Statement: Cardiovascular Monitoring of Children and Adolescents Receiving Psychotropic Drugs. However, no specific cardiovascular monitoring was recommended for the use of stimulant medications. Warnings from the U. S. Food and Drug Administration (FDA) about stimulant medications and public concern for the safety of using them have prompted the current statement.
Studies have shown that stimulant medications like those used to treat ADHD can increase heart rate and blood pressure. These side effects are insignificant for most children with ADHD; however, they're an important consideration for children who have a heart condition. Certain heart conditions increase the risk for sudden cardiac death (SCD), which occurs when the heart rhythm becomes erratic and doesn't pump blood through the body.
Doctors usually use a physical exam and the patient and family history to detect the risk for or presence of health problems before beginning new treatments, including prescribing medication. But some of the cardiac conditions associated with SCD may not be noticed in a routine physical exam. Many of these conditions are subtle and do not result in symptoms or have symptoms that are vague such as palpitations, fainting or chest pain.
That's why the statement writing group recommends adding an ECG to pre-treatment evaluations for children with ADHD. An ECG measures the heart's electrical activity and can often identify heart rhythm abnormalities such as those that can lead to sudden cardiac death.
"After ADHD is diagnosed, but before therapy with a stimulant or other medication is begun, we suggest that an ECG be added to the pre-treatment evaluation to increase the likelihood of identifying cardiac conditions that may place the child at risk for sudden death," said Victoria L. Vetter, M.D., head of the statement writing committee and Professor of Pediatrics at the University of Pennsylvania School of Medicine in Philadelphia.
Vetter also said doctors should evaluate children and adolescents already taking these medications if they were not evaluated when they started the treatment.
If heart problems are suspected after the evaluation, children should be referred to a pediatric cardiologist. Once stimulant treatment begins, children should have their heart health monitored periodically, with a blood pressure check within one to three months, then again at routine follow-ups every six to 12 months.
"Children can have undiagnosed heart conditions without showing symptoms," Vetter said. "Furthermore, a child's body changes constantly, with some conditions not appearing until adolescence."
If the initial ECG was taken before age 12 years, it may be useful to do a repeat ECG after the child is over age 12 years, the statement says.
Widespread use of ECGs to detect heart abnormalities, including screenings for competitive athletes, is not routinely recommended by the American Heart Association. However, the writing group found using ECG screening in this specific population of children prescribed ADHD medication is medically indicated and reasonably priced. That said, however, lack of an ECG shouldn't mean that kids who need ADHD treatment can't get it.
"While we feel that an ECG is reasonable and helpful as a tool to identify children with cardiac conditions that can lead to SCD, if, in the view of their physician, a child requires immediate treatment with stimulant medications, this recommendation is not meant to keep them from getting that treatment," said Vetter, who added that some children may not have access to a pediatric cardiologist who can evaluate an ECG or perform a cardiology consultation.
In 2003, an estimated 2.5 million children took medication for ADHD. Surveys indicate that ADHD affects an estimated 4 percent to 12 percent of all school-aged children in the United States, and it appears more common in children with heart conditions. Studies report that, depending on the specific cardiac condition, 33 percent to 42 percent of pediatric cardiac patients have ADHD, Vetter said. The number of undiagnosed children with heart conditions is unknown as routine heart screening is not performed, but Vetter said that a recent pilot study she presented at the American Heart Association's 2007 Scientific Session indicated that up to 2 percent of healthy school aged children had potentially serious undiagnosed cardiac conditions identified by an ECG.
Data from the FDA showed that between 1999 and 2004, 19 children taking ADHD medications died suddenly and 26 children experienced cardiovascular events such as strokes, cardiac arrests and heart palpitations. Since February 2007, the FDA has required all manufacturers of drug products approved for ADHD treatment to develop Medication Guidelines to alert patients to possible cardiovascular risks.
Future studies are necessary to assess the true risk of SCD in association with stimulant drugs in children and adolescents with and without heart disease, Vetter said. However, studying SCD associated with drugs is difficult because the government's reporting system is voluntary, which means local data on these types of deaths isn't always reported nationally.
A registry of SCD events is necessary for further investigating this issue, the writing committee said. Such a registry would allow for a more accurate understanding of SCD, including the true incidence of it and the potential effectiveness of universal ECG testing and pre-participation screening questionnaires.
The statement writing committee said its recommendations are not intended to limit the appropriate use of stimulants in children with ADHD.
"Our intention is to provide the physician with some tools to help identify heart conditions in children with ADHD, and help them make decisions about the use of stimulant medications and the follow-up of children who take them," Vetter said. "The goal is to allow treatment of ADHD, while attempting to lower the cardiac risk of these products in susceptible children."
Death Rates Decline Following Coronary Bypass Surgery Regardless Of Hospital Volume
Rates of death following coronary artery bypass graft (CABG) surgery have declined since 1997 while the number of procedures performed has decreased, according to a new report. This suggests that the volume of CABG procedures performed at a given facility may not be a reliable predictor of how patients will fare following the surgery.
"The relationship between increased hospital CABG volume and lower mortality has been consistently observed in the clinical literature," the authors write as background information in the article. "The robustness of this association has led some investigators to suggest that postsurgical morbidity [illness] and mortality [death] could be reduced substantially if hospitals with little working experience in cardiac techniques stopped performing procedures such as CABG."
Rocco Ricciardi, M.D., M.P.H., then of the University of Minnesota, Minneapolis, and now of Lahey Clinic, Tufts University, Burlington, Mass., and colleagues analyzed hospital discharge data from a random sample of 108,087,386 patients admitted to U.S. hospitals between 1988 and 2003. A total of 1,082,218 (1 percent) underwent CABG, while 186,483 received heart valve replacement and repair and 1,589,942 received percutaneous transluminal coronary intervention, another procedure used to treat coronary artery disease. "During our 16-year study period, the rate of CABG increased from 7.2 cases per 1,000 discharges in 1988 to 12.2 cases in 1997 but then decreased to 9.1 cases in 2003, while the rate of percutaneous interventions tripled," the authors write.
"For CABG, the proportion of high-volume hospitals declined from 32.5 percent in 1997 to 15.5 percent in 2003," they continue. Despite this shift, the in-hospital death rate following CABG decreased from 5.4 percent in 1988 to 3.3 percent in 2003. Hospitals performing the fewest CABG procedures experienced the largest decreases in death rates.
The findings suggest that improved quality practices may have disseminated to all facilities performing CABG, the authors note. In addition, lower death rates may have remained constant at previously high-volume hospitals that began performing fewer CABG procedures.
"Our data indicate that in-hospital mortality rates and, possibly, quality care practices are improving everywhere independent of CABG volume," the authors write. "This finding should challenge the setting of any arbitrary volume cut point: positive effects on patient outcome are multifactorial and are inadequately described by procedure volume. In addition, the in-hospital mortality rate after CABG may have diminished to such low levels that it is no longer a useful marker of quality."
"The relationship between increased hospital CABG volume and lower mortality has been consistently observed in the clinical literature," the authors write as background information in the article. "The robustness of this association has led some investigators to suggest that postsurgical morbidity [illness] and mortality [death] could be reduced substantially if hospitals with little working experience in cardiac techniques stopped performing procedures such as CABG."
Rocco Ricciardi, M.D., M.P.H., then of the University of Minnesota, Minneapolis, and now of Lahey Clinic, Tufts University, Burlington, Mass., and colleagues analyzed hospital discharge data from a random sample of 108,087,386 patients admitted to U.S. hospitals between 1988 and 2003. A total of 1,082,218 (1 percent) underwent CABG, while 186,483 received heart valve replacement and repair and 1,589,942 received percutaneous transluminal coronary intervention, another procedure used to treat coronary artery disease. "During our 16-year study period, the rate of CABG increased from 7.2 cases per 1,000 discharges in 1988 to 12.2 cases in 1997 but then decreased to 9.1 cases in 2003, while the rate of percutaneous interventions tripled," the authors write.
"For CABG, the proportion of high-volume hospitals declined from 32.5 percent in 1997 to 15.5 percent in 2003," they continue. Despite this shift, the in-hospital death rate following CABG decreased from 5.4 percent in 1988 to 3.3 percent in 2003. Hospitals performing the fewest CABG procedures experienced the largest decreases in death rates.
The findings suggest that improved quality practices may have disseminated to all facilities performing CABG, the authors note. In addition, lower death rates may have remained constant at previously high-volume hospitals that began performing fewer CABG procedures.
"Our data indicate that in-hospital mortality rates and, possibly, quality care practices are improving everywhere independent of CABG volume," the authors write. "This finding should challenge the setting of any arbitrary volume cut point: positive effects on patient outcome are multifactorial and are inadequately described by procedure volume. In addition, the in-hospital mortality rate after CABG may have diminished to such low levels that it is no longer a useful marker of quality."
Patients Arriving At Hospitals In Off Hours Get Slower, Less Care
Patients hospitalized with heart attacks tend to get faster and more comprehensive care if they arrive during daytime hours, according to a new report. But, researchers said, variations in care don't seem to impact in-hospital death rates.
"Previous studies looking at how patients' hospital arrival time for heart attack impacts medical care and outcomes have shown mixed results," said Hani Jneid, M.D., lead author of the study and an interventional cardiology physician-in-training at the Massachusetts General Hospital in Boston.
To determine how hospital arrival time might impact heart attack patients' care and outcomes, Jneid and colleagues examined data on 62,814 heart attack patients in the American Heart Association's Get With The Guidelines--Coronary Artery Disease (GWTG-CAD) database.
"The Get With The Guidelines database is a powerful research tool," Jneid said. "It is a contemporary national clinical registry, which includes a variety of hospitals, including teaching and non-teaching, rural and urban, from all regions of the United States."
The researchers examined differences in medical care and in-hospital death among heart attack patients admitted during regular hours (7 a.m.-7 p.m. weekdays) versus off hours (7 p.m.-7 a.m. weeknights, weekends and holidays).
Of the patients studied, 54 percent arrived during off hours. After adjusting for baseline characteristics, patients arriving during off hours were 7 percent less likely to undergo primary percutaneous coronary intervention (PCI) and 6 percent less likely to undergo PCI or another type of revascularization called coronary artery bypass graft (CABG) compared with patients arriving during regular hours.
"Emergency angioplasty, or PCI, is the preferred procedure after an ST-segment elevation myocardial infarction, which is a heart attack caused by a completely blocked artery," Jneid said.
"The goal of PCI is to open the artery as soon as possible and preferably within 90 minutes of the patient arriving at the emergency room.
"In our study, the average time from when the patient entered the hospital to when he or she received the procedure was 110 minutes during off hours compared with 85 minutes during regular hours."
The researchers also found that arrival during off hours was associated with 66 percent lower odds of achieving the 90-minute window for primary angioplasty that the American College of Cardiology and American Heart Association recommend.
Despite the differences, however, the rate of in-hospital death was similar among patients arriving during off-hours (7.1 percent) versus regular hours (7.2 percent). These findings were similar in men and women and among all age subgroups.
"It is particularly interesting to note that the observed delays in primary PCI did not translate into measurable differences in in-hospital outcome," Jneid said. "This seems to run counter to previous study findings. Future studies should not only strive to confirm or disprove these results, but also examine variables that might affect the interplay of care and outcome with arrival time.
"This represents a vital opportunity for physicians to improve care, and is particularly important from a public health standpoint," Jneid said. "Our findings should compel healthcare providers and policy makers to work towards reducing the existing disparities in cardiac care with respect to arrival time, and improve healthcare delivery at all times through multifaceted initiatives aiming to improve the timely delivery of evidence-based therapies."
"Previous studies looking at how patients' hospital arrival time for heart attack impacts medical care and outcomes have shown mixed results," said Hani Jneid, M.D., lead author of the study and an interventional cardiology physician-in-training at the Massachusetts General Hospital in Boston.
To determine how hospital arrival time might impact heart attack patients' care and outcomes, Jneid and colleagues examined data on 62,814 heart attack patients in the American Heart Association's Get With The Guidelines--Coronary Artery Disease (GWTG-CAD) database.
"The Get With The Guidelines database is a powerful research tool," Jneid said. "It is a contemporary national clinical registry, which includes a variety of hospitals, including teaching and non-teaching, rural and urban, from all regions of the United States."
The researchers examined differences in medical care and in-hospital death among heart attack patients admitted during regular hours (7 a.m.-7 p.m. weekdays) versus off hours (7 p.m.-7 a.m. weeknights, weekends and holidays).
Of the patients studied, 54 percent arrived during off hours. After adjusting for baseline characteristics, patients arriving during off hours were 7 percent less likely to undergo primary percutaneous coronary intervention (PCI) and 6 percent less likely to undergo PCI or another type of revascularization called coronary artery bypass graft (CABG) compared with patients arriving during regular hours.
"Emergency angioplasty, or PCI, is the preferred procedure after an ST-segment elevation myocardial infarction, which is a heart attack caused by a completely blocked artery," Jneid said.
"The goal of PCI is to open the artery as soon as possible and preferably within 90 minutes of the patient arriving at the emergency room.
"In our study, the average time from when the patient entered the hospital to when he or she received the procedure was 110 minutes during off hours compared with 85 minutes during regular hours."
The researchers also found that arrival during off hours was associated with 66 percent lower odds of achieving the 90-minute window for primary angioplasty that the American College of Cardiology and American Heart Association recommend.
Despite the differences, however, the rate of in-hospital death was similar among patients arriving during off-hours (7.1 percent) versus regular hours (7.2 percent). These findings were similar in men and women and among all age subgroups.
"It is particularly interesting to note that the observed delays in primary PCI did not translate into measurable differences in in-hospital outcome," Jneid said. "This seems to run counter to previous study findings. Future studies should not only strive to confirm or disprove these results, but also examine variables that might affect the interplay of care and outcome with arrival time.
"This represents a vital opportunity for physicians to improve care, and is particularly important from a public health standpoint," Jneid said. "Our findings should compel healthcare providers and policy makers to work towards reducing the existing disparities in cardiac care with respect to arrival time, and improve healthcare delivery at all times through multifaceted initiatives aiming to improve the timely delivery of evidence-based therapies."
Readily Available Treatment Could Help Prevent Heart Disease In Kidney Patients, Study Suggests
The estimated 19 million Americans living with chronic kidney disease (CKD) face a high risk of death from cardiovascular disease. Recent studies have shown that a main source of this cardiovascular risk is CKD patients' high levels of blood phosphate.
Now researchers at Washington University School of Medicine in St. Louis have demonstrated that high blood phosphate directly stimulates calcification of blood vessels and that phosphate-binding drugs can decrease vascular calcification. That means drugs that reduce phosphate levels could help protect CKD patients from cardiovascular disease, according to the authors of the study, which is available online in advance of print publication in the Journal of the American Society of Nephrology.
"One of the kidney's functions is to help maintain a constant balance of phosphate in the bloodstream," says senior author Keith A. Hruska, M.D., director of the Division of Pediatric Nephrology and professor of pediatrics, of medicine and of cell biology and physiology. "When kidney failure occurs, an excess of serum phosphate develops. It turns out that high phosphate serves as a signal that stimulates cells within blood vessel walls to become bone-forming cells and to deposit calcium crystals. That produces vascular stiffness that is a cause of cardiovascular mortality."
Phosphate-binding drugs are already on the market, and based on evidence in this study and others like it, the Food and Drug Administration has recently decided to extend the label of such drugs. As a result, calcium acetate (PhosLo), sevelamer (Renagel) and lanthanum carbonate (Fosrenol) will be labeled to indicate they are approved for treatment of high serum phosphate levels in patients with CKD.
Hruska, Suresh Mathew, M.D., instructor in pediatrics, and colleagues studied mice with CKD and atherosclerosis -- calcified plaques in the arteries. They gave the mice phosphate-binding agents, which prevent phosphate in the diet from entering the bloodstream. This therapy decreased arterial calcification in the mice. The treatment also diminished the activity of a genetic program that stimulates blood vessel cells to become bone-forming cells.
Skeletal turnover normally allows the bones to assimilate excess phosphate, but in people with CKD, bone turnover is inhibited and excess phosphate stays in the bloodstream. There it can induce the differentiation of blood-vessel-wall cells into bone-forming cells.
Scientists previously identified a growth factor called BMP-7 (bone morphogenic factor-7) that increases skeletal bone formation. In addition to demonstrating the beneficial effect of phosphate-binding drugs, Hruska and colleagues found that giving BMP-7 to CKD mice also reduced phosphate in their bloodstreams and decreased the calcification of blood vessels.
"BMP-7 restores the ability of the skeleton to serve as a reservoir for phosphate, and in the walls of blood vessels it blocks the process of differentiation into bone-forming cells," Hruska says. "It's possible that BMP-7 also could someday be developed into a therapy for patients with CKD and have the added advantage of restoring normal skeletal function and protecting the normal physiology of blood vessels."
Hruska indicates that large-scale population studies have demonstrated that serum phosphate levels may be as important as serum cholesterol levels in predicting cardiovascular problems. The mechanism described in the study, in which the skeleton cannot absorb excess phosphates, is also present in elderly people with osteoporosis. In addition, diabetes can lead to kidney damage and high serum phosphate.
"There's a huge segment of the population affected by these problems," Mathew says. "Elderly osteoporosis patients and people with diabetes have high rates of cardiovascular disease and high levels of vascular calcification. So our findings may have importance even beyond patients with CKD."
Because the data in this study strongly suggest serum phosphate reduction could be highly effective for reducing cardiovascular risk in CKD patients, Hruska and Mathew have begun the process of establishing a clinical trial of phosphate reduction in CKD. "We're working to design a multicenter study to demonstrate that control of phosphate balance in CKD decreases cardiovascular events and increases survival," Hruska says.
Journal reference: Mathew S, Tustison K, Sugatani T, Chaudhary L, Rifas L, Hruska K. The mechanism of phosphorus as a cardiovascular risk factor in chronic kidney disease. Journal of the American Society of Nephrology, April 16, 2008 (advance online publication).
Funding from the National Institutes of Health, Shire, Johnson & Johnson and Genzyme supported this research.
Now researchers at Washington University School of Medicine in St. Louis have demonstrated that high blood phosphate directly stimulates calcification of blood vessels and that phosphate-binding drugs can decrease vascular calcification. That means drugs that reduce phosphate levels could help protect CKD patients from cardiovascular disease, according to the authors of the study, which is available online in advance of print publication in the Journal of the American Society of Nephrology.
"One of the kidney's functions is to help maintain a constant balance of phosphate in the bloodstream," says senior author Keith A. Hruska, M.D., director of the Division of Pediatric Nephrology and professor of pediatrics, of medicine and of cell biology and physiology. "When kidney failure occurs, an excess of serum phosphate develops. It turns out that high phosphate serves as a signal that stimulates cells within blood vessel walls to become bone-forming cells and to deposit calcium crystals. That produces vascular stiffness that is a cause of cardiovascular mortality."
Phosphate-binding drugs are already on the market, and based on evidence in this study and others like it, the Food and Drug Administration has recently decided to extend the label of such drugs. As a result, calcium acetate (PhosLo), sevelamer (Renagel) and lanthanum carbonate (Fosrenol) will be labeled to indicate they are approved for treatment of high serum phosphate levels in patients with CKD.
Hruska, Suresh Mathew, M.D., instructor in pediatrics, and colleagues studied mice with CKD and atherosclerosis -- calcified plaques in the arteries. They gave the mice phosphate-binding agents, which prevent phosphate in the diet from entering the bloodstream. This therapy decreased arterial calcification in the mice. The treatment also diminished the activity of a genetic program that stimulates blood vessel cells to become bone-forming cells.
Skeletal turnover normally allows the bones to assimilate excess phosphate, but in people with CKD, bone turnover is inhibited and excess phosphate stays in the bloodstream. There it can induce the differentiation of blood-vessel-wall cells into bone-forming cells.
Scientists previously identified a growth factor called BMP-7 (bone morphogenic factor-7) that increases skeletal bone formation. In addition to demonstrating the beneficial effect of phosphate-binding drugs, Hruska and colleagues found that giving BMP-7 to CKD mice also reduced phosphate in their bloodstreams and decreased the calcification of blood vessels.
"BMP-7 restores the ability of the skeleton to serve as a reservoir for phosphate, and in the walls of blood vessels it blocks the process of differentiation into bone-forming cells," Hruska says. "It's possible that BMP-7 also could someday be developed into a therapy for patients with CKD and have the added advantage of restoring normal skeletal function and protecting the normal physiology of blood vessels."
Hruska indicates that large-scale population studies have demonstrated that serum phosphate levels may be as important as serum cholesterol levels in predicting cardiovascular problems. The mechanism described in the study, in which the skeleton cannot absorb excess phosphates, is also present in elderly people with osteoporosis. In addition, diabetes can lead to kidney damage and high serum phosphate.
"There's a huge segment of the population affected by these problems," Mathew says. "Elderly osteoporosis patients and people with diabetes have high rates of cardiovascular disease and high levels of vascular calcification. So our findings may have importance even beyond patients with CKD."
Because the data in this study strongly suggest serum phosphate reduction could be highly effective for reducing cardiovascular risk in CKD patients, Hruska and Mathew have begun the process of establishing a clinical trial of phosphate reduction in CKD. "We're working to design a multicenter study to demonstrate that control of phosphate balance in CKD decreases cardiovascular events and increases survival," Hruska says.
Journal reference: Mathew S, Tustison K, Sugatani T, Chaudhary L, Rifas L, Hruska K. The mechanism of phosphorus as a cardiovascular risk factor in chronic kidney disease. Journal of the American Society of Nephrology, April 16, 2008 (advance online publication).
Funding from the National Institutes of Health, Shire, Johnson & Johnson and Genzyme supported this research.
New Genetic Links To Psoriasis Uncovered
In the first comprehensive study of the genetic basis of psoriasis, researchers at Washington University School of Medicine in St. Louis have discovered seven new sites of common DNA variation that increase the risk of the troublesome skin condition. They also found that variations in one genetic region link psoriasis and a related joint disorder, psoriatic arthritis, to four autoimmune diseases: type 1 diabetes, Grave's disease, celiac disease and rheumatoid arthritis.
"Common diseases like psoriasis are incredibly complex at the genetic level," says lead investigator Anne Bowcock, Ph.D., professor of genetics at the School of Medicine. "Our research shows that small but common DNA differences are important in the development of psoriasis. Although each variation makes only a small contribution to the disease, patients usually have a number of different genetic variations that increases their risk of psoriasis and psoriatic arthritis."
The DNA variations uncovered by the researchers point to different biological pathways that underlie psoriasis and may eventually lead to new targeted drugs and treatments that hit specific pathways, Bowcock says.
An estimated 7 million Americans have psoriasis, an autoimmune disease that occurs when the body's immune cells mistakenly attack the skin. The condition is characterized by red, scaly patches that can be itchy, painful or both. Some 10 to 30 percent of patients with psoriasis develop psoriatic arthritis, a condition that is often excruciatingly painful and debilitating.
The Washington University researchers focused on points of common variation in the genome called single nucleotide polymorphisms, or SNPs. While most of the 3 billion nucleotides that comprise DNA are thought to be identical from one person to the next, some 10 million SNPs build variation into the genome and make each individual unique. Some of these SNPs play a crucial role in a person's predisposition to disease or good health.
Using an approach known as whole genome association, the investigators scanned more than 300,000 SNPs in the genomes of 223 psoriasis patients, including 91 who had psoriatic arthritis. They compared the DNA variations in people with psoriasis to those found in 519 healthy control patients, looking for specific differences that may be linked to the disease. They then replicated their findings in a larger set of patients -- 577 with psoriasis and 576 with psoriatic arthritis -- and more than 1,200 healthy controls.
Bowcock and her team found seven novel DNA variations linked to psoriasis. Four other variations associated with the disease that had been identified previously by other researchers also were confirmed by the current study.
Whole genome association studies have recently been used to identify common genetic variations that increase the risk of diseases such as breast cancer, heart disease and type 2 diabetes. They typically involve more than 1,000 patients with a particular disease to help ensure that the genetic variations identified in the study do not occur by chance. While the current study included fewer patients, nearly half of them had a sibling and, in some cases, a parent with psoriasis, which increases the odds of finding genetic variations that contribute to the disease.
The researchers found the strongest genetic risk for psoriasis lies in a region of the genome that contains the major histocompatibility complex, a collection of genes involved in distinguishing the body's own cells from foreign invaders. "Although this region has been known to play a major role in psoriasis, DNA variations in the MHC alone have been known to not be enough to trigger disease," Bowcock says. "Only 10 percent of patients with variations in the major histocompatibility complex developed psoriasis. This tells us that other genetic or environmental factors also contribute to the disease."
One MHC variation linked to psoriasis and psoriatic arthritis occurs in the gene HCP5, the scientists noted. That variation was recently reported to delay the onset of AIDS in people infected with HIV. This is particularly interesting, Bowcock says, because psoriasis can be triggered by infection with HIV or other viruses. It may be that in people with this SNP variant, viral infection triggers a larger immune response that slows the development of AIDS but also leads to excessive inflammation in the skin and bone joints in genetically susceptible individuals, leading to the onset of psoriasis and psoriatic arthritis.
Notably, DNA variations on chromosome 4 were strongly linked to psoriatic arthritis. These same variations were also associated with psoriasis and had been previously linked to type 1 diabetes, rheumatoid arthritis, Grave's disease (caused by an overproductive thyroid gland) and celiac disease (caused by the inability to digest gluten). "Doctors have noticed that some psoriasis patients have autoimmune diseases such as celiac disease, Grave's disease, and type 1 diabetes," Bowcock says. "But we didn't know whether this was a coincidence. Now we know there is a genetic component underlying all of these diseases."
The same region of chromosome 4 contains genes that code for the signaling molecules IL2 and IL21. This opens the door to investigating whether existing drugs that block either molecule may be effective in some psoriasis patients, especially those with psoriatic arthritis.
The researchers also uncovered significant DNA variations on chromosome 13 in a genetic region involved in modifying proteins, and on chromosome 15, in a region responsible for producing a protein that activates TNF alpha (tumor necrosis factor-alpha) in a specialized immune cell known as a dendritic cell. While TNF alpha normally helps fight infections, it is thought to be a major player in psoriasis and psoriatic arthritis. Several FDA-approved psoriasis medications work by binding to TNF-alpha, thereby preventing it from communicating with cells.
Bowcock is now involved in a larger genome-wide association study of psoriasis patients and says she expects it will uncover additional genetic variations that are associated with psoriasis.
Eventually, she predicts, such studies will lead to more effective, better-targeted therapies.
"The goal of this study and other genome-association studies is to get to personalized medicine, where you can diagnose a disease and ask what genetic risk factors this person has that points to altered pathways," she says. "Then, we can target those pathways for specific therapeutic interventions."
Journal reference: Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A, Malloy MJ, Pullinger C, Kane J, Saccone S, Worthington J, Bruce I, Kwok P-Y, Menter A, Krueger J, Barton A, Saccone NL, Bowcock AM. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. Public Library of Science Genetics. April 4, 2008.
The research was supported by grants from the National Institutes of Health.
"Common diseases like psoriasis are incredibly complex at the genetic level," says lead investigator Anne Bowcock, Ph.D., professor of genetics at the School of Medicine. "Our research shows that small but common DNA differences are important in the development of psoriasis. Although each variation makes only a small contribution to the disease, patients usually have a number of different genetic variations that increases their risk of psoriasis and psoriatic arthritis."
The DNA variations uncovered by the researchers point to different biological pathways that underlie psoriasis and may eventually lead to new targeted drugs and treatments that hit specific pathways, Bowcock says.
An estimated 7 million Americans have psoriasis, an autoimmune disease that occurs when the body's immune cells mistakenly attack the skin. The condition is characterized by red, scaly patches that can be itchy, painful or both. Some 10 to 30 percent of patients with psoriasis develop psoriatic arthritis, a condition that is often excruciatingly painful and debilitating.
The Washington University researchers focused on points of common variation in the genome called single nucleotide polymorphisms, or SNPs. While most of the 3 billion nucleotides that comprise DNA are thought to be identical from one person to the next, some 10 million SNPs build variation into the genome and make each individual unique. Some of these SNPs play a crucial role in a person's predisposition to disease or good health.
Using an approach known as whole genome association, the investigators scanned more than 300,000 SNPs in the genomes of 223 psoriasis patients, including 91 who had psoriatic arthritis. They compared the DNA variations in people with psoriasis to those found in 519 healthy control patients, looking for specific differences that may be linked to the disease. They then replicated their findings in a larger set of patients -- 577 with psoriasis and 576 with psoriatic arthritis -- and more than 1,200 healthy controls.
Bowcock and her team found seven novel DNA variations linked to psoriasis. Four other variations associated with the disease that had been identified previously by other researchers also were confirmed by the current study.
Whole genome association studies have recently been used to identify common genetic variations that increase the risk of diseases such as breast cancer, heart disease and type 2 diabetes. They typically involve more than 1,000 patients with a particular disease to help ensure that the genetic variations identified in the study do not occur by chance. While the current study included fewer patients, nearly half of them had a sibling and, in some cases, a parent with psoriasis, which increases the odds of finding genetic variations that contribute to the disease.
The researchers found the strongest genetic risk for psoriasis lies in a region of the genome that contains the major histocompatibility complex, a collection of genes involved in distinguishing the body's own cells from foreign invaders. "Although this region has been known to play a major role in psoriasis, DNA variations in the MHC alone have been known to not be enough to trigger disease," Bowcock says. "Only 10 percent of patients with variations in the major histocompatibility complex developed psoriasis. This tells us that other genetic or environmental factors also contribute to the disease."
One MHC variation linked to psoriasis and psoriatic arthritis occurs in the gene HCP5, the scientists noted. That variation was recently reported to delay the onset of AIDS in people infected with HIV. This is particularly interesting, Bowcock says, because psoriasis can be triggered by infection with HIV or other viruses. It may be that in people with this SNP variant, viral infection triggers a larger immune response that slows the development of AIDS but also leads to excessive inflammation in the skin and bone joints in genetically susceptible individuals, leading to the onset of psoriasis and psoriatic arthritis.
Notably, DNA variations on chromosome 4 were strongly linked to psoriatic arthritis. These same variations were also associated with psoriasis and had been previously linked to type 1 diabetes, rheumatoid arthritis, Grave's disease (caused by an overproductive thyroid gland) and celiac disease (caused by the inability to digest gluten). "Doctors have noticed that some psoriasis patients have autoimmune diseases such as celiac disease, Grave's disease, and type 1 diabetes," Bowcock says. "But we didn't know whether this was a coincidence. Now we know there is a genetic component underlying all of these diseases."
The same region of chromosome 4 contains genes that code for the signaling molecules IL2 and IL21. This opens the door to investigating whether existing drugs that block either molecule may be effective in some psoriasis patients, especially those with psoriatic arthritis.
The researchers also uncovered significant DNA variations on chromosome 13 in a genetic region involved in modifying proteins, and on chromosome 15, in a region responsible for producing a protein that activates TNF alpha (tumor necrosis factor-alpha) in a specialized immune cell known as a dendritic cell. While TNF alpha normally helps fight infections, it is thought to be a major player in psoriasis and psoriatic arthritis. Several FDA-approved psoriasis medications work by binding to TNF-alpha, thereby preventing it from communicating with cells.
Bowcock is now involved in a larger genome-wide association study of psoriasis patients and says she expects it will uncover additional genetic variations that are associated with psoriasis.
Eventually, she predicts, such studies will lead to more effective, better-targeted therapies.
"The goal of this study and other genome-association studies is to get to personalized medicine, where you can diagnose a disease and ask what genetic risk factors this person has that points to altered pathways," she says. "Then, we can target those pathways for specific therapeutic interventions."
Journal reference: Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A, Malloy MJ, Pullinger C, Kane J, Saccone S, Worthington J, Bruce I, Kwok P-Y, Menter A, Krueger J, Barton A, Saccone NL, Bowcock AM. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. Public Library of Science Genetics. April 4, 2008.
The research was supported by grants from the National Institutes of Health.
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