Sensitivity to Others' Feelings Underdeveloped in Teen Brain, Studies Show

Sept. 7, 2006 -- It may be a "me first" world in the typical teen brain.

Brain scans show that teen's brains may still be developing when it comes to sensitivity to other people's feelings.

And in a second study, the same researchers found that adolescents and preadolescents are slower at predicting how another person might feel in a given situation.

Sarah-Jayne Blakemore, PhD, of University College London, worked on the two studies.

"We think that a teenager's judgment of what they would do in a given situation is driven by the simple question: 'What would I do?'" Blakemore says, in a University College London news release.

"Adults, on the other hand, ask: "What would I do, given how I would feel and given how the people around me would feel as a result of my actions?'" she continues.

Blakemore presented the findings from the studies today in Norwich, England, at the BA Festival of Science, held by the British Association for the Advancement of Science.

What Would You Do?

In the brain scan study, Blakemore's team looked at 19 teen girls and 20 women in London.

The teens were nearly 15 years old, on average, and attended a selective private school. The women were 28 years old, on average, and were university students or graduates.

Each girl or woman viewed a series of questions displayed on a computer screen.

Some questions were "What would you do?" scenarios that required an intentional choice, such as: "You are at the cinema and have trouble seeing the screen. Do you move to another seat?"

Other questions focused on cause and effect, such as: "A huge tree suddenly comes crashing down in a forest. Does it make a loud noise?"

Participants answered "likely" or "not likely" to each question by pressing a computer key.

Meanwhile, their brains were scanned with magnetic resonance imaging (MRI).

Teen Brain, Adult Brain

The brain scans showed different areas of brain activity on the questions involving personal choice.

The teens' brain scans showed more activity at the superior temporal sulcus located towards the back of brain, while the adults' brain scans showed more activity in the medial prefrontal cortex located towards the front of the brain.

"These results suggest that the neural strategy for thinking about intentions changes during adolescence," the researchers write.

Brain activity on the Nature-related questions was similar for teens and adults, the scans showed.

In the second study presented today, Blakemore's team found that preadolescent (average age 8.6 years) and adolescent (average age, 13) boys and girls were slower than adults to answer questions about how a fictional character might feel in certain situations.

In that study, 74 preadolescents and adolescents were compared with 38 adults (average age 24). The researchers found the adults were quicker at choosing how a third person might feel in a described situation.

No Teen Bashing

The findings don't mean all teens are insensitive, or that all adults are empathetic.

But adults do seem more sensitive to other people's feelings, and their brain scans appear to back that up, according to Blakemore and colleagues.

Of course, grown-ups have an advantage: They're older than teens.

Experience may nudge the brain to become more sensitive to other people's feelings, the researchers note.

So, insensitive teens may not stay that way.

Blakemore's team can't say how or when teens' sensitivity skills develop.




Saludos Cordiales
Dr. José Manuel Ferrer Guerra

Gender-Specific Disparities in Obesity

Gender-Specific Disparities in Obesity




Tyrone F. Borders, PhD; James E. Rohrer, PhD; Kathryn M. Cardarelli, PhD

Abstract and Introduction

Abstract

Little prior research has investigated whether the correlates of obesity differ between men and women. The objective of this study was to examine gender-specific disparities in obesity by rurality of residence, race/ethnicity, and socioeconomic status. Particular emphasis was devoted to examining potential differences between residents of urban, suburban, and rural areas. Data from the adult version of the 2003 Behavioral Risk Factor Surveillance System (BRFSS) for the state of Texas were used to model the crude and adjusted odds of being obese as compared to normal weight. The findings showed that males of other race/ethnicity had lower adjusted odds of obesity than non-Hispanic whites, but other race/ethnicity was insignificant for females. Females who were Hispanic or black/African American had higher adjusted odds of obesity than non-Hispanic whites, but Hispanic ethnicity and black/ African American race were insignificant for males. Men and women residing in non-metropolitan areas had higher adjusted odds of obesity than their counterparts in metropolitan areas. No economic disparities were revealed among men, but females with high household income had lower odds of obesity than those with low income. Educational status was insignificant for men and women. The findings suggest that programs and policies aimed at curbing obesity should target males and females residing in non-metropolitan localities. Other initiatives should focus on particular groups of women, including those who are Hispanic or black/ African American and have low household income.

Introduction

Obesity is frequently cited as one of America's more pressing public health problems. Although its incidence appears to be steadying,[1] a substantial proportion of adult Americans remain obese. According to estimates from the 2001-2002 National Health and Nutrition Examination

Survey (NHANES), 27.3 percent of adult Americans are moderately or severely obese.[1] Obesity is of national public health concern not only because of its exorbitant prevalence, but also because of its deleterious effects on health status. Several studies have linked obesity to an increased risk of chronic disease,[2] poor health-related quality of life,[3,4] and functional disability.[5] In fact, the public health impact of obesity has been shown to exceed that of two other behavioral problems, smoking and heavy alcohol use.[4]

Because obesity can be considered a personal behavioral choice, one could argue that public interventions are unwarranted. An important argument in favor of governmental involvement concerns the substantial costs attributable to obesity, which have been estimated to range between 5.3 and 5.7 percent of overall Medical care expenditures.[6,7] The Medical care spending associated with obesity is notably higher among members of the government-funded Medicaid (6.7 percent) and Medicare (6.5 percent) insurance programs.[7]

As public health policy makers and practitioners expand programs aimed at combating obesity, additional research is needed to identify high risk population subgroups. Prior research has indicated that residents of rural areas, ethnic and racial minorities, and persons with low socioeconomic status are particularly vulnerable to health problems and the federal government has placed a great deal of emphasis on research and programs aimed at reducing such disparities.[8,9] A report by the U.S. Surgeon General described disparities in the prevalence of obesity,[10] but with the exception of a few studies conducted in the United States[11] and other countries,[12-15] a dearth of research has investigated disparities after adjusting for potential confounders. The present study examined differences in obesity according to rurality of residence, ethnicity or race, and socioeconomic status after controlling for extraneous demographic, social, behavioral, and psychological variables. Because prior research has revealed sex differences in the predictors of obesity,[12] separate models were tested for males and females.

Methods

Data

The data source was the 2003 Behavioral Risk Factor Surveillance System (BRFSS) for the state of Texas. The BRFSS is conducted on an annual basis by the Texas Department of Health in coordination with the Centers for Disease Control and Prevention. A unique aspect of the Texas BRFSS data set used in this study is its inclusion of a variable reflecting the rurality of residence. Over a 12-month period, 6,035 non-institutionalized, civilian adult Texans were sampled via random-digit dialing. The participation rate, calculated as the proportion of individuals who were contacted via the phone and completed the survey, was 70 percent. If fewer than 5 percent of the cases for a given independent variable had missing values, that variable was excluded from the analyses. Cases that had missing BMI values (n = 379) were also excluded, resulting in final unweighted and weighted sample sizes of 5,078 and 13,387,565.

Measures

Body mass index (BMI) was calculated according to self-reports of height and weight and then categorized as underweight (BMI ≤18.5), normal weight (18.5 > BMI < 25), overweight (≥25 BMI < 30), obese (BMI ≥30), and BMI missing. Obese and normal weight persons were compared under the assumption that the achievement of normal weight is a public health goal.

Disparities variables were race/ethnicity (non-Hispanic white vs. Hispanic, black/African American, and other race/ethnicity), rurality of residence (metropolitan central city, metropolitan suburban, and non-metropolitan), household income (<$25,000 vs. $25,000 to $74,999, $75,000 or more, and income missing), and educational status (less than a high school degree vs. A high school degree, some college, and college graduate or more education). Most health-related studies only distinguish metropolitan and non-metropolitan status, which could fail to accurately differentiate residents of urban, suburban, and rural areas. We therefore used a trichotomous classification of metropolitan-central city (an urban core county containing 50,000 or more person), metropolitan-suburban (a metropolitan county adjacent to a core metropolitan-central city area), and non-metropolitan (all other counties). The income missing dummy variable was created to retain those cases that had missing values, an approach that has been used in several prior studies.[16-18]

Control variables included demographic, social, behavioral, and psychological characteristics. Demographic variables were sex (Male vs. Female) and age category (18-24 vs. 25-34, 35-44, 45-54, 55-64, and ≥65). Social variables included marital status (married vs. Single), the number of children in the household (none vs. 1-2 and ≥3), and employment/ working status (employed/working vs unemployed not working). Prior research has demonstrated that the number of children is related to women's weight status.[19-21] Behavioral characteristics included smoking and exercise. In the BRFSS, respondents were asked whether they had ever smoked and, if so, whether they smoked cigarettes every day, some days, or not at all. Responses were recategorized to distinguish current (smoke every day or some days) and past smokers. Respondents were also asked several questions about their physical activity during a usual week: if they engage in moderate physical activity (PA) at least ten minutes at a time, if they engage in vigorous PA for at least ten minutes, the number of times per week the engage in PA, and the total time per day they engage in PA. Federal guidelines recommend at least 30 minutes of moderate exercise for 5 days per week or 20 minutes of vigorous exercise for 3 days per week.[22] Three exercise groups were computed: none, some, and meets recommendations. Self-rated mental health was assessed with the following question: ''Now, thinking about your mental health, which includes stress, depression and problems with emotions, for how many days during the past 30 days was your mental health not good?'' Poor self-rated mental health was defined as having 14 or more days of ''not good'' mental health.

Statistical Analyses

STATA 8.0[23] was used to conduct descriptive and multivariate analyses and account for the complex sampling scheme and population weights. The frequency of each disparities variable and covariate (demographic, social, behavioral, and psychological factors) was calculated for normal weight and obese individuals. Univariate and multivariate logistic models were conducted by gender. Univariate logistic regression analyses were conducted to model the association between each disparities variable and obesity, respectively. Multivariate logistic regression analyses were conducted to model the association between each disparities variable and obesity while adjusting for demographic, social, behavioral, and psychological covariates.

Results
Of the 5,078 respondents included in the analyses, 36.48 percent were normal weight and 25.03 percent were obese. While not reported in the table, 2.13 percent were underweight and 36.36 percent were over-weight. Disparities variables and demographic and social covariates are shown for the overall sample and for normal weight and obese individuals in Table 1 . Behavioral and psychological covariates are shown for the overall sample and by BMI status in Table 2 .

Although the findings are not reported in the tables presented in this paper, we did test for differences in the odds of obesity between men and women. Males were found to have increased crude (OR = 1.27, 95% CI = 1.07, 1.50) and adjusted odds (OR = 1.63, CI = 1.36, 1.96) of obesity as compared to females.

Table 3 shows crude and adjusted odds of obesity for the disparities variables by gender. Among males, Hispanic ethnicity and black/African American race were not significantly associated with obesity. However, other race/ethnicity was significantly associated with lower crude and adjusted odds of moderate obesity as compared to non-Hispanic whites. The findings for females were noticeably different. Compared to non-His-panic white females, Hispanic and black/African American females had higher crude and adjusted odds of obesity. Other race/ethnicity was insignificant for females.

Males living in non-metropolitan areas had higher crude and adjusted odds of moderate obesity than males living in metropolitan-central city areas. Similarly, females residing in non-metropolitan areas had higher adjusted, but not crude, odds of obesity than females residing in metropolitan-central city areas. There were no significant differences between males or females residing in metropolitan-central city and suburban areas.

The associations between income and obesity differed between males and females. Among males, those who had household incomes of $25,000 to $74,999 had higher crude, but not adjusted, odds of obesity as compared to those with incomes of $25,000 or less. Females with household incomes of $75,000 or more had lower crude and adjusted moderate odds of obesity.

Educational status was insignificant at the 0.05 alpha level in the models for females and males. However, having a college degree or more education was associated with lower adjusted odds of obesity at the 0.10 level for males and females.

Discussion

Despite much recent attention devoted to health disparities in the United States,[10] little research has investigated differences in obesity according to rurality of residence, race or ethnicity, and socioeconomic status (SES). A limited number of studies foreign to the United States have examined the social and economic correlates of obesity,[12-15] but whether their findings are relevant to Americans is questionable, especially because of cross-country differences in ethnic and racial composition. Analyses of the National Health and Nutrition Examination Survey (NHANES) have demonstrated disparities in the prevalence of obesity by race, ethnicity, and economic status,[24] but have not controlled for the full range of factors known to influence obesity, including exercise and mental health. A recent study using data from the National Health Interview Survey (NHIS) examined differences in obesity by the rurality of residence while controlling for selected confounders, but did not stratify analyses by gender.[11] Thus, the present study lends further insight into gender-specific disparities in obesity.

Regardless of gender, residents of non-metropolitan counties appear to have a somewhat higher risk of obesity than persons residing in metropolitan areas. This finding is supported by at least one national[11] and a limited number of state or regionally specific studies.[25-27] Higher rates of obesity among rural residents may be attributable to poor health behaviors which extend from childhood to adulthood, including poor dietary intake[28] and sedentary lifestyles.[11,29] Others have speculated that a general shift from farming to manufacturing-based economies in rural areas explains the higher prevalence of obesity among rural residents.[30]

According to our data, race and income are stronger risk factors for obesity among women than non-metropolitan residence. As mentioned earlier, Hispanic and black/African American females were more likely to be obese than non-Hispanic whites, even when controlling for other potential factors. Similarly, descriptive findings from the NHANES indicate that Mexican-American and black/African American women have a lower prevalence of overweight and obesity than their non-Hispanic white counterparts.[10,24] Yet, the findings for men were noticeably different. Possible explanations include racial or ethnic differences in body image expectations. For example, in Texas, perhaps the thin idea is more common among non-Hispanic white women. On the other hand, the Male-beauty ideal of a large torso may apply to all races and ethnic groups.

Higher household income protected females against obesity, but not males. This finding is coherent with other studies that consistently find an inverse association between high SES and obesity among women, but not men.[31,32] One possible explanation for such a difference may be that family and social pressures to conform to a certain body image exert a stronger influence in women of higher SES.[32] Another explanation is that women of higher SES are more likely to engage in preventive health behavior, such as regular exercise and better diet, compared to their Male counterparts.[33] Finally, women of higher SES may be less likely to have high parity,[34] which is associated with overweight and obesity.[20,21] In a population-based study of Swedish women, investigators found that of the factors that accounted for the SES-obesity association, reproductive history (chiefly, early menarche and high parity) was the strongest explanatory factor, accounting for 44 percent of the variance.[35]

Because we focused on the state of Texas, the generalizability of the findings may be limited to areas with similar geographic, demographic, and social characteristics. However, because the CDC mandates that each state conduct the BRFSS on an annual basis, health researchers in states other than Texas could replicate our analyses to identify subgroups of their own populations which have a high risk of obesity. To facilitate similar comparisons in other states or for the nation as a whole, the CDC and affiliated state agencies will need to provide indicators of rural, suburban, and urban residence (most states do not make such indicators publicly available). Another drawback to the BRFSS is that it relies on self-reports of height and weight, which are used to calculate BMI. Prior research based on the national sample of BRFSS respondents suggests that self-reports are less valid than objective height and weight measures,[36] although the reliability of the BRFSS measures for height, weight, and BMI were found to have correlation coefficients of 0.84 to 0.94.[37] Other national telephone surveys have yielded prevalence rates similar to those from the NHANES,[4] suggesting that valid estimates of BMI can be obtained through self reports. Because our primary objective was not to estimate the prevalence of obesity in Texas, whether the Texas BRFSS accurately represents adult Texans is of less concern than whether the associations found in the present study are valid. Despite the aforementioned limitations of the BRFSS, it remains the most feasible means of evaluating health problems at the state level.

In summary, our findings support that some programs should be directed toward residents of non-metropolitan areas. The main thrust of the obesity campaign should selectively target specific groups of men and women, particularly Hispanic, black/African-American, and poor females. Targeting these risk groups is not only more efficient, but allows for the implementation of tailored interventions.

Reprint Address

Tyrone F.Borders, PhD Department of Health Policy and Management, Fay W. Boozman College of Public Health, 4301 W. Markham St., Slot 820, Little Rock, AR 72205-7199; e-mail: tfborders@uams.edu




Enviado por Dr. José Manuel Ferrer Guerra

IAC: Dyslipidemia in Children Abated by Switched Regimens

By Ed Susman, MedPage Today Staff Writer
Reviewed by Robert Jasmer, MD; Assistant Professor of Medicine, University of California, San Francisco
August 14, 2006

Explain to parents that side effects with antiretroviral drugs impact children's lipid profiles as well as adults being treated with those drugs.


Note that body changes in children are difficult to observe because of the on-going Nature of their development.


This study was published as an abstract and presented at an industry-sponsored symposium conference. These data were not peer-reviewed.
TORONTO, Aug. 14 -- Children treated for HIV infection are at increased risk of dyslipidemia, but a switch in regimens may dampen the impact of those metabolic changes.

In a mini-satellite symposium held in conjunction with the 16th International AIDS Conference, Alessandra Vigano, M.D., chief of pediatrics infectious disease at the University of Milan in Italy reviewed studies that involved long-term treatment of children with highly active antiretroviral therapy (HAART).


"This population is particularly vulnerable because children are growing and are likely to have long-term exposure to highly active antiretroviral therapy," Dr. Vigano said during the Bristol-Myers Squibb Canada-sponsored symposium, Metabolic Complications: New Insights and Evolving Management Strategies.


Various studies have shown that abnormalities in lipids occur 13% to 52% of the time in all patients taking combination antiretroviral therapy. Dr. Vigano suggested that these abnormalities occur more frequently in children with lipodystrophy and that the phenomenon is associated with protease inhibitors.


She cited one European study in which 280 children ages three to 18 underwent lipid testing. The median age of the children was nine. She said that study found that 27% of those children had hypercholesterolemia with levels of cholesterol greater than 200 mg/dl. She also said the study found that 21% of the children had elevated triglycerides, and 10% of them had both high cholesterol and high triglycerides.


In a study that Dr. Vigano reported in 2005, 14 children were switched from a regimen of Zerit (stavudine), Epivir (lamivudine), and a protease inhibitor to a New regimen of Viread (tenofovir), Epivir and Sustiva (efavirenz) in a 48-week randomized trial.


At the start of the trial nearly half the children were in the 95th percentile of cholesterol level. After 48 weeks, none of the children was in the 95th percentile. After 12 weeks on the New regimen, there were less than 10% of the children in the 95th percentile.


The story was similar for triglycerides with the percentage of children in the 95th percentile falling from 42% at baseline to less than 10% after 48 weeks.


In a 96-week study, 24 children were switched from Zerit to Viread and from a protease inhibitor to Sustiva. "Switching from Zerit to Viread was associated with restoration of physiological fat accrual and a lack of lipoatrophy progression." Dr. Vigano said.


"These changes may well yield possible positive effects on pubertal development, fertility, psychological wellness and normal lipid and glucose metabolism," she said.


While the studies indicate that treatment changes can alter unhealthy lipid abnormalities in children, Dr. Vigano noted that there has been little research on the subject. "Data on the long-term consequences of these metabolic complications are lacking," she said. "An important goal in treating pediatric HIV-infection will be to design drugs with fewer side effects or to better mange those of the current drugs."

Primary source: 16th International AIDS Conference



Enviado por Dr. José Manuel Ferrer Guerra

Autism May Involve A Lack Of Connections And Coordination In Separate Areas Of The Brain, Researchers Find

Researchers have found in two studies that autism may involve a lack of connections and coordination in separate areas of the brain.

In people with autism, the brain areas that perform complex analysis appear less likely to work together during problem solving tasks than in people who do not have the disorder, report researchers working in a network funded by the National Institutes of Health. The researchers found that communications between these higher-order centers in the brains of people with autism appear to be directly related to the thickness of the anatomical connections between them.

In a separate report, the same research team found that, in people with autism, brain areas normally associated with visual tasks also appear to be active during language-related tasks, providing evidence to explain a bias towards visual thinking common in autism.

"These findings provide support to a New theory that views autism as a failure of brain regions to communicate with each other," said Duane Alexander, M.D., Director of NIH's National Institute of Child Health and Human Development. "The findings may one day provide the basis for improved treatments for autism that stimulate communication between brain areas."

The studies and the theory are the work of Marcel Just, Ph.D., D.O. Hebb Professor of Psychology at Carnegie Mellon University in Pittsburgh, Pennsylvania, and Nancy Minshew, M.D.., Professor of Psychiatry and Neurology at the University of Pittsburgh School of Medicine and their colleagues. The research was conducted by the Collaborative Program of Excellence in Autism, a research network funded by the NICHD and the National Institute on Deafness and Other Communication Disorders.

People with autism often have difficulty communicating and interacting socially with other people. The saying "unable to see the forest for the trees" describes how people with autism frequently excel at details, yet struggle to comprehend the larger picture. For example, some children with autism may become spelling bee champions, but have difficulty understanding the meaning of a sentence or a story.

An earlier finding by these researchers described how a group of people with autism tended to use parts of the brain typically associated with processing shapes to remember letters of the alphabet. A news release detailing that finding appears at http://www.nichd.nih.gov/new/releases/final_autism.cfm.

Participants with autism in both current studies had normal I.Q. There were no significant differences between the participants with and without autism in age or I.Q.

The first of the two New studies recently was published online in the Journal Cerebral Cortex. In that study, the researchers used a brain imaging technique known as functional magnetic resonance imaging, or fMRI, to view the brains of people with autism as well as a comparison group of people who do not have autism. All of the study participants were asked to complete the Tower of London test. The task involves moving three balls into a specified arrangement in an array of three receptacles. The Tower of London is used to gauge the functioning of the prefrontal cortex.

This brain area, located in the front, upper part of the brain, deals with strategic planning and problem-solving. The prefrontal cortex is the executive area of the brain, in which decision making, judgment, and impulse control reside.

A little further back is the parietal cortex, which controls high-level visual thinking and visual imagery, supporting the visual aspects of the problem-solving. Both the prefrontal and parietal cortex play a critical part in performing the Tower of London test.

In the normal participants, the prefrontal cortex and the parietal cortex tended to function in synchrony (increasing and decreasing their activity at the same time) while solving the Tower of London task. This suggests that the two brain areas were working together to solve the problem.

In the participants with autism, however, the two brain areas, prefrontal and parietal, were less likely to function in synchrony while working on the task.

The researchers made another discovery, for the first time finding a relationship between this lower level of synchrony and the properties of some of the neurological "cables" or white matter fiber tracts that connect brain areas.

White matter consists of fibers that, like cabling, connect brain areas. The largest of the white matter tracts is known as the corpus callosum, which allows communication between the two hemispheres (halves) of the brain.
"The size of the corpus callosum was smaller in the group with autism, suggesting that inter-regional brain cabling is disrupted in autism," Dr.. Just said.

In essence, the extent to which the two key brain areas (prefrontal and parietal) of the autistic participants worked in synchrony was correlated with the size of the corpus callosum. The smaller the corpus callosum, the less likely the two areas were to function in synchrony. In the normal participants, however, the size of the corpus callosum did not appear to be correlated with the ability of the two areas to work in synchrony.

"This finding provides strong evidence that autism is a disorder involving the biological connections and the coordination of processing between brain areas," Dr. Just said.

He added, however, that the thickness, or extent, of connections between brain areas may not be the basis for the disorder. Although the neurological connections between the prefrontal cortex appear to be reduced in autism, the brains of people with autism have thicker connections between certain brain regions within each hemisphere.

"At this point, we can say that autism appears to be a disorder of abnormal neurological and informational connections of the brain, but we can't yet explain the nature of that abnormality," Dr. Just said.

In the second study, published online in the journal Brain, the researchers examined the extent to which brain areas involved in language interact with brain regions that process images. Dr. Just explained that earlier studies, as well as anecdotal accounts, suggest that people with autism rely more heavily on visual and spatial areas of the brain than do other people.

In this study, the researchers used fMRI to examine brain functioning in participants with autism and in normal participants during a true-false test involving reading sentences with low imagery content and high imagery content. A typical low imagery sentence consisted of constructions like "Addition, subtraction, and multiplication are all math skills." A high imagery sentence, "The number eight when rotated 90 degrees looks like a pair of eyeglasses," would first activate left prefrontal brain areas involved with language, and then would involve parietal areas dealing with vision and imagery as the study participant mentally manipulated the number eight.

As the researchers expected, the visual brain areas of the normal participants were active only when evaluating sentences with imagery content. In contrast, the visual centers in the brains of participants with autism were active when evaluating both high imagery and low imagery sentences.

"The heavy reliance on visualization in people with autism may be an adaptation to compensate for a diminished ability to call on prefrontal regions of the brain," Dr. Just said.

The second study also confirmed the observations in the first study--that the prefrontal and parietal brain regions of the cortex in people with autism were less likely to work in synchrony than were the brains of normal volunteers. The second study also confirmed that the extent to which the two parts of the cortex could work together was correlated with the size of the corpus callosum that connected them. Dr. Just and his colleagues are conducting additional studies to ascertain the nature of the abnormality of the connections in the brains of people with autism.

###

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute's Web site at http://www.nichd.nih.gov/.

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.


Saludos Cordiales
Dr. José Manuel Ferrer Guerra

Cystic Fibrosis-related Diabetes Studied By UF

A growing number of cystic fibrosis patients are battling a second, often deadly complication: a unique form of diabetes that shares characteristics of the type 1 and type 2 versions that strike many Americans.

Many of these patients are teens who take enzymes to help digest their food and undergo daily physical therapy to loosen the thick, sticky mucus that clogs their lungs. But despite treatments that are helping thousands to live decades longer than ever before, when diabetes strikes, their life expectancy plummets -- on average by two years for men and an astounding 16 for women.

Now a University of Florida study in animals suggests diabetes in cystic fibrosis patients is not caused by the destruction of insulin-producing cells in the pancreas -- as is often the case in patients with the traditional form of type 1 diabetes -- but by differences in how these cells function. The findings were published this month in the American Diabetes Association's Journal Diabetes.

Cystic fibrosis patients with diabetes produce some insulin on their own, but they require daily injections to boost their levels when eating so they can properly use sugar and other food nutrients for energy. At times they also become very resistant to the insulin they do make, similar to people with type 2 diabetes.

"For the longest time, the development of diabetes in cystic fibrosis has been thought to be chronic destruction of pancreas, so eventually you get loss of the insulin-producing beta cells," said Michael Stalvey, M.D., an assistant professor of pediatrics at UF. "Our study provides some early evidence to suggest there is an inherent difference in beta cell function."

Cystic fibrosis patients suffer recurrent episodes of infection and inflammation that slowly destroy the lungs. The pancreas is also affected, interfering with proper digestion. The disease stems from a faulty gene that blocks the normal passage of salt and water through the body's cells. It is this gene deficiency that is proposed to cause insulin-producing cells to malfunction, Stalvey said.

About 30,000 Americans have cystic fibrosis, making it the nation's most common lethal hereditary disorder. On average, they will not live past 35, though some are living through their 40s and even into their 60s. As each year passes, the likelihood they will develop diabetes increases. As many as 16 percent of all patients with cystic fibrosis also have diabetes, a number that is expected to rise as overall life expectancy for cystic fibrosis patients increases. Half will show signs of diabetes by age 30 and will suffer a rapid decline in overall health and lung function, muscle mass and body mass index.

"It's becoming more and more frequent because of the increasing age of patients," Stalvey said. "That's part of the reason why New recommendations call for screening patients 14 years and older yearly with an oral glucose tolerance test. Each year we know their likelihood of developing diabetes gets higher and higher.

"These young people, teenagers or young adults in their early 20s, have been fighting all their lives to stay healthy and keep their nutrition up," he added. "Now they've just been given something that potentially will overwhelm them. It's a huge thing for them, given the consequences that diabetes means to their underlying condition."

In the UF study, researchers developed the first animal model for the study of cystic fibrosis-related diabetes. They used mice that scientists from the University of North Carolina engineered to be missing the gene that makes the protein responsible for transporting salt and water across the cell membrane. People with cystic fibrosis have a mutated form of this protein.

UF scientists administered a low dose of a chemotherapy drug that weakened insulin-producing cells but did not destroy them. They then tested the animals' ability to regulate their blood sugar while fasting and after receiving glucose, simulating the rise in blood sugar that occurs after eating food.

Animals with the protein deficiency were more sensitive to the effects of the chemotherapy drug and had more difficulty regulating blood sugar levels, both while fasting and after receiving glucose. Mice that were still able to produce the crucial protein that prevents cystic fibrosis were able to maintain normal blood sugar levels, even after the drug had damaged some of their insulin-producing cells.

"This goes beyond improving our understanding of patients with cystic fibrosis-related diabetes; it also will help us improve our understanding of other forms of diabetes and help us work on strategies for a future cure," Stalvey said.

"Twenty-five percent of adolescents and 40 percent of adults with cystic fibrosis have diabetes, and diabetes is associated with poorer survival in this population," said Antoinette Moran, M.D., division head of pediatric endocrinology and director of the Pediatric Diabetes Program at the University of Minnesota Medical School. "The cause of cystic fibrosis-related diabetes is not completely understood, but it is clearly different from other forms of diabetes. The study by Stalvey and colleagues is important because it is the first to show that there are intrinsic abnormalities in the insulin-producing cells of the pancreas related to the genetic defect that causes cystic fibrosis."

###

Stalvey's collaborators included Desmond Schatz, M.D., Terence Flotte, M.D., and Mark Atkinson, Ph.D. The study was supported in part by the Lawson Wilkins Pediatric Endocrinology Society, the Cystic Fibrosis Foundation and the National Institutes of Health.

Contact: Melanie Fridl Ross
University of Florida




Saludos Cordiales
Dr. José Manuel Ferrer Guerra

IAC: Dyslipidemia in Children Abated by Switched Regimens

By Ed Susman, Contributing Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Assistant Professor of Medicine, University of California, San Francisco
August 14, 2006

Explain to parents that side effects with antiretroviral drugs impact children's lipid profiles as well as adults being treated with those drugs.


Note that body changes in children are difficult to observe because of the on-going Nature of their development.


This study was published as an abstract and presented at an industry-sponsored symposium conference. These data were not peer-reviewed.



TORONTO, Aug. 14 -- Children treated for HIV infection are at increased risk of dyslipidemia, but a switch in regimens may dampen the impact of those metabolic changes.

In a mini-satellite symposium held in conjunction with the 16th International AIDS Conference, Alessandra Vigano, M.D., chief of pediatrics infectious disease at the University of Milan in Italy reviewed studies that involved long-term treatment of children with highly active antiretroviral therapy (HAART).


"This population is particularly vulnerable because children are growing and are likely to have long-term exposure to highly active antiretroviral therapy," Dr. Vigano said during the Bristol-Myers Squibb Canada-sponsored symposium, Metabolic Complications: New Insights and Evolving Management Strategies.


Various studies have shown that abnormalities in lipids occur 13% to 52% of the time in all patients taking combination antiretroviral therapy. Dr. Vigano suggested that these abnormalities occur more frequently in children with lipodystrophy and that the phenomenon is associated with protease inhibitors.


She cited one European study in which 280 children ages three to 18 underwent lipid testing. The median age of the children was nine. She said that study found that 27% of those children had hypercholesterolemia with levels of cholesterol greater than 200 mg/dl. She also said the study found that 21% of the children had elevated triglycerides, and 10% of them had both high cholesterol and high triglycerides.


In a study that Dr. Vigano reported in 2005, 14 children were switched from a regimen of Zerit (stavudine), Epivir (lamivudine), and a protease inhibitor to a New regimen of Viread (tenofovir), Epivir and Sustiva (efavirenz) in a 48-week randomized trial.


At the start of the trial nearly half the children were in the 95th percentile of cholesterol level. After 48 weeks, none of the children was in the 95th percentile. After 12 weeks on the New regimen, there were less than 10% of the children in the 95th percentile.


The story was similar for triglycerides with the percentage of children in the 95th percentile falling from 42% at baseline to less than 10% after 48 weeks.


In a 96-week study, 24 children were switched from Zerit to Viread and from a protease inhibitor to Sustiva. "Switching from Zerit to Viread was associated with restoration of physiological fat accrual and a lack of lipoatrophy progression." Dr. Vigano said.


"These changes may well yield possible positive effects on pubertal development, fertility, psychological wellness and normal lipid and glucose metabolism," she said.


While the studies indicate that treatment changes can alter unhealthy lipid abnormalities in children, Dr. Vigano noted that there has been little research on the subject. "Data on the long-term consequences of these metabolic complications are lacking," she said. "An important goal in treating pediatric HIV-infection will be to design drugs with fewer side effects or to better mange those of the current drugs."

Primary source: 16th International AIDS Conference

Is Insomnia a Marker for Psychiatric Disorders in General Hospitals?

Rocha FL, Hara C, Rodrigues CV, et al
Sleep Med. 2005; [Epub ahead of print]

This study assessed the frequency of insomnia in a general Medical hospital and its relationship to psychiatric comorbidity.

Study Design
A total of 200 adult patients (50.5% men) in a 293-bed general hospital provided information about symptoms of insomnia with a structured and codified questionnaire. Patients were asked whether they had difficulty initiating sleep, sleep maintenance problems, early-morning awakening, or interference with functioning in the previous 30 days. To assess the presence of psychiatric disease, the investigators administered the Portuguese version of the Mini-International Neuropsychiatric Interview (MINI).

Results
More than half (56.5%) of the patients complained of insomnia. Insomnia was not mentioned in any of these patients' hospital records, and this symptom predated the hospitalization in many cases. The presence of insomnia was not associated with age, sex, marital status, schooling, or personal income.

Half of the 200 patients reported having a history of or a current psychiatric disorder, the most common of which was major depressive disorder (35%). The presence of insomnia had a positive predictive value for major depressive disorder of 46.9%. All the patients with major depressive disorder were symptomatic during the hospitalization.

Other psychiatric disorders identified were generalized anxiety disorder (11.5%), panic disorder/agoraphobia (9%), alcohol abuse/dependence (7.5%), psychotic syndrome (5.5%), bipolar disorder (5.5%), social phobia (4%), posttraumatic stress disorder (4%), obsessive-compulsive disorder (4%), dysthymic disorder (2%), and substance abuse/dependence (1%). Only 3 (1.5%) of the patients in this study had any record of their psychiatric diagnosis in the hospital chart.

Conclusion
Hospitalized patients with insomnia have 3.6 times the risk of major depressive disorder, which is often unrecognized.

Commentary
Insomnia reportedly affects more than one third of hospitalized patients. Given the stress of hospitalization, a hostile sleeping environment, and the discomfort of Medical ailments and treatments, it is surprising that this number is not much higher. Nonetheless, caregivers often overlook insomnia as a treatable problem, and in this study, insomnia was not even mentioned in the hospital charts of any of the patients. In addition, many patients in general hospitals experience comorbid psychiatric disease, which is also unrecognized, as it was in this study.

Improving sleep in hospitalized patients may have salutary effects on recuperation from Medical illness. Similarly, major depression may adversely affect morbidity, mortality, and hospitalization time, and should be identified and treated. Because of the strong association between insomnia and major depression, patients who complain of insomnia should receive a psychiatric assessment.


Saludos Cordiales
Dr. José Manuel Ferrer Guerra

New England Journal Of Medicine Damaged By Its Conduct Over Vioxx, Says Former Editor Of British Medical Journal

The conduct of the New England Journal of Medicine (NEJM) in the dispute involving the VIGOR trial and the drug Vioxx has raised doubts about the Journal's integrity, according to a former editor of the BMJ.

Writing in next month's Journal of the Royal Society of Medicine, Richard Smith questions the conduct of the NEJM and in particular editorial decisions which delayed the publication of corrections in the Journal.

Commenting on his article, Dr Smith said: “It is unfortunate that the New England Journal of Medicine waited five years before publishing a correction to its VIGOR study, which was published in November 2000. Concerns about the correctness of the study were raised with the NEJM's editor, Jeff Drazen, as early as August 2001, the drug was withdrawn in 2004 and yet it wasn't until December 2005 that the Journal published its first correction.”

“The Journal has suggested that all the correct data were available on the Food and Drug Administration website but, in my view, that is not good enough. Doctors, pharmacists and health professionals do not obtain their information by searching through copious data on the FDA website; they get it from leading journals,” he said.

“The Journal failed its readers. It has damaged its reputation,” Dr Smith added.

Before Vioxx was withdrawn from the market, Merck bought 900,000 reprints of the article from the NEJM at an estimated cost of US$700,000 - $830,000 to use in promoting the drug.

The VIGOR (Vioxx Gastrointestinal Outcomes Research Study) trial involved 8000 patients who received naproxen or rofecoxib (Vioxx), a Cox-2 inhibitor expected to have fewer gastrointestinal side effects than common non-steroidal anti-inflammatory drugs (NSAIDs). Patients given naproxen experienced 121 side effects compared with 56 in patients taking rofecoxib. Vioxx was voluntarily withdrawn by Merck in 2004 in the light of evidence suggesting it increased the risk of heart attacks and stroke.

Lapses at the New England Medical Journal [PDF 45k]

‘Lapses at the New England Medical Journal' by R Smith is published in the August 2006 issue (Vol. 99) of the Journal of the Royal Society of Medicine. JRSM is the flagship Journal of the Royal Society of Medicine. It has been published continuously since 1809. Its Editor is Dr Kamran Abbasi.

The article is available free at http://www.jrsm.org.


Saludos Cordiales
Dr. José Manuel Ferrer Guerra

Exercise Improves Physical Health, Quality Of Life For Breast Cancer Survivors

Researchers at The University of Texas M. D. Anderson Cancer Center have found that exercise decreases pain and helps breast cancer survivors feel healthier and increase participation in daily activities.

The Active for Life after Breast Cancer Study, published Friday in the Journal, Patient Education and Counseling, evaluated the effect of exercise on former cancer patients' physical well-being.

Approximately 60 breast cancer survivors, randomly placed in a lifestyle intervention group or a standard care control group, participated in the six-month, 21-session study. Researchers taught participants to incorporate short periods of moderate exercise into their daily routines, which included 30 minutes of physical exercise at least five days per week.

According to Karen Basen-Engquist, Ph.D., principal investigator of the study and associate professor of behavioral science at M. D. Anderson Cancer Center, study leaders informed participants that they should still be able to talk while exercising at a moderate level, but they should not be able to sing during the activity. Lifestyle intervention participants met weekly for four months and then semi-weekly for two months to learn cognitive and behavioral skills to support effective behavioral change.

Study leaders emphasized that physical activity need not be an organized, lengthy endeavor, but rather a lifestyle activity that could include vacuuming, brisk walking or climbing stairs rather than taking the elevator.

"The wonderful take-away message from this study is that simple exercises, such as walking during coffee breaks or parking further away from work, can have beneficial effects on physical health and functioning," said Basen-Engquist. "Exercise doesn't need to be a daunting activity or even an organized outing to reap significant rewards for breast cancer survivors."

The study examined barriers to increasing physical activity, including time restraints, other commitments, fatigue, pain or muscle problems, incontinence, hot flashes and premature menopause due to chemotherapy.

"We found that exercise improved participants' ability to perform certain physical tasks, increased self reports of feeling healthy and decreased pain and the degree to which their activities were limited by physical health problems," said Basen-Engquist.

She notes that study leaders invited participation from a pool of breast cancer survivors who had recently completed both radiation and chemotherapy. Women who maintained primarily sedentary lifestyles were chosen as ideal candidates "because we wanted to see if through the study they would integrate exercise into their daily lives," said Basen-Engquist.

Researchers at M. D. Anderson Cancer Center partnered with the Kelsey Research Foundation, a non-profit organization dedicated to improving the quality of patient care and health outcomes through research and education; Kelsey-Seybold, a large, multi-specialty health care clinic; the Houston chapter of the Sisters' Network, a support and advocacy group for African-American breast cancer survivors; and The Rose, a Houston non-profit agency that sponsors support groups for breast cancer survivors, in recruiting study participants.

"One of the goals of our cancer program is to improve the quality of life of our cancer survivors," said Anthony Greisinger, Ph.D., executive director of the Kelsey Research Foundation. "Our staff was encouraged by Dr. Basen-Engquist's positive findings and we hope to evaluate this exercise intervention in a larger study with M. D. Anderson Cancer Center."

At baseline and again six months later, researchers administered physical and emotional assessments using self-report questionnaires, five physical performance tests and seven-day physical activity recall interviews.

At the conclusion of the study, researchers asked both the lifestyle intervention group and the standard care control group to walk as far as possible in six minutes. Participants who received lifestyle intervention training showed significant physical improvement, walking an average of 100 feet further than their control group peers.

Additionally, those in the intervention group made substantial progress incorporating exercise as a habit throughout the day, while the control group only began to make such changes.

Roslyn Smith, a study participant and M. D. Anderson Cancer Center employee, reports improved post-treatment physical health and quality of life. "I learned about exercises I could do at my desk, as well as the benefits of walking around the institution for added fitness. The fight to maintain a healthy life style is an ongoing one, but one that I must pursue. After attending recent lectures on the great advantages of yoga, I'm excited about having another avenue to help me stay active," said Smith.

###

Basen-Engquist is encouraged by the study's positive findings and notes that - if the lifestyle approach is shown to be effective in a larger randomized trial - it represents a highly practical intervention that easily can be delivered to breast cancer survivors by health care institutions or community organizations without dedicated exercise facilities and equipment.

Contact: Claire Tyson
University of Texas M. D. Anderson Cancer Center




Saludos Cordiales
Dr. José Manuel Ferrer Guerra

Committee for Medicinal Products for Human Use Post-authorisation Summary of Opinion for Lyrica

Pregabalin

LONDON, July 27, 2006-On 27 July 2006 the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion?? To recommend the variation to the terms of the marketing authorisation for the medicinal product Lyrica. The Marketing Authorisation Holder for this medicinal product is Pfizer Limited.

The New indication adopted by CHMP is: "Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults."

Detailed conditions for the use of this product will be described in the updated Summary of Product Characteristics (SPC) which will be published in the revised European Public Assessment Report (EPAR) and will be available in all official European Union languages after the variation to the marketing authorisation has been granted by the European Commission.

For information, the full indication of Lyrica will be as follows???:

"Neuropathic pain

Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults.

Epilepsy

Lyrica is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalisation.

Generalised Anxiety Disorder

LYRICA is indicated for the treatment of Generalised Anxiety Disorder (GAD) in adults."

Saludos Cordiales

Dr. José Manuel Ferrer Guerra

Sleep Disturbance in Mild to Moderate Alzheimer's Disease

Andrew N. Wilner, MD, FAAN, FACP


From
Sleep Medicine
July 2005 (Volume 6, Number 4)

Sleep Disturbance in Mild to Moderate Alzheimer's Disease
Moran M, Lynch CA, Walsh C, Coen R, Coakley D, Lawlor BA
Sleep Med. 2005;6:347-352

This study assessed the frequency of sleep disturbances in patients with Alzheimer's disease with the Behavioral Pathology in Alzheimer's disease (BEHAVE-AD) rating scale. The investigators compared behavioral and psychological symptoms of patients with and without sleep disturbances.

Study Design
The study authors retrospectively reviewed the case records of 224 patients (70.1% women; mean age, 74.9) with probable Alzheimer's disease seen at The Mercer's Institute for Research on Ageing, a national referral Center in Ireland.

The BEHAVE-AD rating scale includes 3 questions regarding sleep. Patients who experienced any of these symptoms in the previous month were considered to have a sleep disturbance: (1) repetitive wakenings, (2) 50% to 75% of former sleep cycle, and (3) less than 50% of former sleep cycle.

The BEHAVE-AD also assesses abnormalities, such as activity disturbance, affective disturbance, aggressiveness, anxieties and phobias, hallucinations, paranoid and delusional ideation, and the global impact of behavioral symptoms on the patient and caregiver. A reliable informant provided the information necessary to complete the BEHAVE-AD.

The investigators also used the Blessed Dementia Scale and Instrumental Activities of Daily Living (IADL) to assess functional impairment, and the Mini-Mental State Examination (MMSE), the Cambridge Examination for Mental Disorders of the Elderly (CAMCOG), and the Clinical Dementia Rating Scale (CDR) to evaluate cognitive impairment.

Results
Fifty-five (24.5%) patients experienced sleep disturbances. Age, sex, the number of patients taking medications, and performance on the MMSE, CAMCOG, Blessed Dementia Scale, and IADL was similar between those who had sleep disturbances and those who did not. However, univariate analysis of the BEHAVE-AD revealed that aggressiveness (verbal outbursts, physical threats, and agitation; P = .0011) and global rating (P = .0041) scores were significantly worse for the patients with sleep disturbances.

Conclusion
In this study, sleep disturbances occurred in 24.5% of patients with Alzheimer's disease and were associated with aggressiveness and troubling behavior.

Commentary
Sleep disturbances in patients with Alzheimer's disease are common, and affect approximately 25% of patients.[1] Patients with Alzheimer's disease who do not sleep well during the night may have episodes of wandering and thus more opportunities for falls and injuries. These patients' inability to sleep at night may cause the primary caregivers, often the spouse, to have a sleepless night as well, adversely affecting his/her ability to provide care. This may explain why nocturnal wandering in patients with Alzheimer's disease is one of the most frequent causes of nursing home placement. Effective treatment of insomnia may improve the quality of life of both the patient and caregiver, delaying nursing home placement.

Although the BEHAVE-AD is not the ideal instrument for assessing the details of sleep initiation and maintenance, it is a reasonable tool in this case because no sleep questionnaire has been validated in patients with dementia.

The conclusions of this study are that aggressiveness and the impact of behavioral disturbances on both the caregiver and the patient (global rating) are associated with sleep disturbances. Clearly, sleepless patients add stress to the caregiver, resulting in a higher global rating. Aggressiveness and sleep disturbances may be part of a common pathophysiology of Alzheimer's disease, or one may worsen the other. The retrospective Nature of this study does not allow one to tease out cause and effect.

Clinicians who treat sleep disturbances in patients with Alzheimer's disease also may wish to evaluate behavioral disturbances. More studies are needed to assess the impact of improved sleep on abnormal behaviors, as well as the impact of treatment of abnormal behaviors on the quality of sleep.



Enviado por Dr. José Manuel Ferrer Guerra

Amikacin Dosing in the Intensive Care Unit

Once-daily Administration (ODA) of aminoglycosides has been a dosing strategy in use for several years.[1,2] The rationale behind ODA Administration is to optimize the pharmacodynamic properties of the aminoglycosides; more specifically, ODA results in a higher peak serum concentration than traditional multiple daily dosing can achieve, which enhances the concentration-dependent bactericidal killing activity of the compound. Additionally, aminoglycosides exhibit a postantibiotic effect which is exerted during the drug-free interval at the end of the ODA interval. During the postantibiotic effect, the organism is essentially stunned and does not replicate.[1,2]

Dosing recommendations for gentamicin/tobramycin for ODA range from 5 to 7 mg/kg, using the higher dose for select critically ill patients, and a multiple of 4 for amikacin (20-28 mg/kg, again using the higher dose for select critically ill patients).[1,3,4]

Critically ill patients have exhibited variability in pharmacokinetics that can require higher dosage requirements.[1,5] Additionally, such patients can experience rapid changes in fluid status and renal function, requiring careful monitoring of serum aminoglycoside concentrations to ensure efficacy and avoid nephrotoxicity. It is recommended to avoid trough amikacin serum concentrations of higher than 5 mcg/mL.[6]

Saludos Cordiales

Dr. José Manuel Ferrer Guerra