A study of the relationship between physical activity and cardiovascular fitness and coronary heart disease risk factors in female adolescents

The association of measures of physical activity with coronary heart disease (CHD) risk factors in children, especially those for atherosclerosis, is unknown. The purpose of this study was to determine the association of physical activity and cardiovascular fitness with blood lipids and lipoproteins in pre-adolescent and adolescent girls.^ The study population was comprised of 131 girls aged 9 to 16 years who participated in the Children's Nutrition Research Center's Adolescent Study. The dependent variables, blood lipids and lipoproteins, were measured by standard techniques. The independent variables were physical activity measured as the difference between total energy expenditure (TEE) and basal metabolic rate (BMR), and cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg). TEE was measured by the doubly-labeled water (DLW) method, and BMR by whole-room calorimetry. Cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg), was measured on a motorized treadmill. The potential confounding variables were sexual maturation (Tanner breast stage), ethnic group, body fat percent, and dietary variables. A systematic strategy for data analysis was used to isolate the effects of physical activity and cardiovascular fitness on blood lipids, beginning with assessment of confounding and interaction. Next, from regression models predicting each blood lipid and controlling for covariables, hypotheses were evaluated by the direction and value of the coefficients for physical activity and cardiovascular fitness.^ The main result was that cardiovascular fitness appeared to be more strongly associated with blood lipids than physical activity. An interaction between cardiovascular fitness and sexual maturation indicated that the effect of cardiovascular fitness on most blood lipids was dependent on the stage of sexual maturation.^ A difference of 760 kcal/d physical activity (which represents the difference between the 25th and 75th percentile of physical activity) was associated with negligible differences in blood lipids. In contrast, a difference in 10 ml/min/kg of VO$\rm\sb{2max}$ or cardiovascular fitness (which represents the difference between the 25th and 75th percentile in cardiovascular fitness) in the early stages of sexual maturation was associated with an average positive difference of 15 mg/100 ml ApoA-1 and 10 mg/100 ml HDL-C. ^

Identification of genes associated with quantitative traits involved in cardiovascular disease and lipoprotein metabolism

Cardiovascular disease (CVD) is a threat to public health. It has been reported to be the leading cause of death in United States. The invention of next generation sequencing (NGS) technology has revolutionized the biomedical research. To investigate NGS data of CVD related quantitative traits would contribute to address the unknown etiology and disease mechanism of CVD. NHLBI's Exome Sequencing Project (ESP) contains CVD related phenotypes and their associated NGS exomes sequence data. Initially, a subset of next generation sequencing data consisting of 13 CVD-related quantitative traits was investigated. Only 6 traits, systolic blood pressure (SBP), diastolic blood pressure (DBP), height, platelet counts, waist circumference, and weight, were analyzed by functional linear model (FLM) and 7 currently existing methods. FLM outperformed all currently existing methods by identifying the highest number of significant genes and had identified 96, 139, 756, 1162, 1106, and 298 genes associated with SBP, DBP, Height, Platelet, Waist, and Weight respectively. ^

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.

A longitudinal comparison of cardiovascular disease risk factors among children and adolescents in the U.S. and Japan: Project HeartBeat!

Blood cholesterol and blood pressure development in childhood and adolescence have important impact on the future adult level of cholesterol and blood pressure, and on increased risk of cardiovascular diseases. The U.S. has higher mortality rates of coronary heart diseases than Japan. A longitudinal comparison in children of risk factor development in the two countries provides more understanding about the causes of cardiovascular disease and its prevention. Such comparisons have not been reported in the past. ^ In Project HeartBeat!, 506 non-Hispanic white, 136 black and 369 Japanese children participated in the study in the U.S. and Japan from 1991 to 1995. A synthetic cohort of ages 8 to 18 years was composed by three cohorts with starting ages at 8, 11, and 14. A multilevel regression model was used for data analysis. ^ The study revealed that the Japanese children had significantly higher slopes of mean total cholesterol (TC) and high density lipoprotein (HDL) cholesterol levels than the U.S. children after adjusting for age and sex. The mean TC level of Japanese children was not significantly different from white and black children. The mean HDL level of Japanese children was significantly higher than white and black children after adjusting for age and sex. The ratio of HDL/TC in Japanese children was significantly higher than in U.S. whites, but not significantly different from the black children. The Japanese group had significantly lower mean diastolic blood pressure phase IV (DBP4) and phase V (DBP5) than the two U.S. groups. The Japanese group also showed significantly higher slopes in systolic blood pressure, DBP5 and DBP4 during the study period than both U.S. groups. The differences were independent from height and body mass index. ^ The study provided the first longitudinal comparison of blood cholesterol and blood pressure between the U.S. and Japanese children and adolescents. It revealed the dynamic process of these factors in the three ethnic groups. ^

Efficacy of quality criteria to identify potentially harmful information: a cross-sectional survey of complementary and alternative medicine web sites.

BACKGROUND: Many users search the Internet for answers to health questions. Complementary and alternative medicine (CAM) is a particularly common search topic. Because many CAM therapies do not require a clinician's prescription, false or misleading CAM information may be more dangerous than information about traditional therapies. Many quality criteria have been suggested to filter out potentially harmful online health information. However, assessing the accuracy of CAM information is uniquely challenging since CAM is generally not supported by conventional literature. OBJECTIVE: The purpose of this study is to determine whether domain-independent technical quality criteria can identify potentially harmful online CAM content. METHODS: We analyzed 150 Web sites retrieved from a search for the three most popular herbs: ginseng, ginkgo and St. John's wort and their purported uses on the ten most commonly used search engines. The presence of technical quality criteria as well as potentially harmful statements (commissions) and vital information that should have been mentioned (omissions) was recorded. RESULTS: Thirty-eight sites (25%) contained statements that could lead to direct physical harm if acted upon. One hundred forty five sites (97%) had omitted information. We found no relationship between technical quality criteria and potentially harmful information. CONCLUSIONS: Current technical quality criteria do not identify potentially harmful CAM information online. Consumers should be warned to use other means of validation or to trust only known sites. Quality criteria that consider the uniqueness of CAM must be developed and validated.

Evaluating the prevalence, content and readability of complementary and alternative medicine (CAM) web pages on the internet.

Complementary and alternative medicine (CAM) use is growing rapidly. As CAM is relatively unregulated, it is important to evaluate the type and availability of CAM information. The goal of this study is to deter-mine the prevalence, content and readability of online CAM information based on searches for arthritis, diabetes and fibromyalgia using four common search engines. Fifty-eight of 599 web pages retrieved by a "condition search" (9.6%) were CAM-oriented. Of 216 CAM pages found by the "condition" and "condition + herbs" searches, 78% were authored by commercial organizations, whose pur-pose involved commerce 69% of the time and 52.3% had no references. Although 98% of the CAM information was intended for consumers, the mean read-ability was at grade level 11. We conclude that consumers searching the web for health information are likely to encounter consumer-oriented CAM advertising, which is difficult to read and is not supported by the conventional literature.

Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule.

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional profiling revealed that celastrol treatment induces a battery of oxidant defense genes in addition to heat shock genes. Celastrol activated the yeast Yap1 oxidant defense transcription factor via the carboxy-terminal redox center that responds to electrophilic compounds. Antioxidant response genes were likewise induced in mammalian cells, demonstrating that the activation of two major cell stress pathways by celastrol is conserved. We report that celastrol's biological effects, including inhibition of glucocorticoid receptor activity, can be blocked by the addition of excess free thiol, suggesting a chemical mechanism for biological activity based on modification of key reactive thiols by this natural product.

Energy beverages: content and safety.

Exercise is making a resurgence in many countries, given its benefits for fitness as well as prevention of obesity. This trend has spawned many supplements that purport to aid performance, muscle growth, and recovery. Initially, sports drinks were developed to provide electrolyte and carbohydrate replacement. Subsequently, energy beverages (EBs) containing stimulants and additives have appeared in most gyms and grocery stores and are being used increasingly by "weekend warriors" and those seeking an edge in an endurance event. Long-term exposure to the various components of EBs may result in significant alterations in the cardiovascular system, and the safety of EBs has not been fully established. For this review, we searched the MEDLINE and EMBASE databases from 1976 through May 2010, using the following keywords: energy beverage, energy drink, power drink, exercise, caffeine, red bull, bitter orange, glucose, ginseng, guarana, and taurine. Evidence regarding the effects of EBs is summarized, and practical recommendations are made to help in answering the patient who asks, "Is it safe for me to drink an energy beverage when I exercise?"

Severe aortic and arterial aneurysms associated with a TGFBR2 mutation.

BACKGROUND: A 24-year-old man presented with previously diagnosed Marfan's syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. INVESTIGATIONS: CT scans, arteriogram, genetic mutation screening of transforming growth factor beta receptors 1 and 2. DIAGNOSIS: Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan's syndrome, but was later rediagnosed with Loeys-Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. MANAGEMENT: Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease.

History of Medicine Schedule and Abstracts 2009-2010

From Genes to Genome: An historical perspective (David Wheeler) Ignaz Semmelweis: Medical Prophet Without Honor (Ronald L. Young) Why Lewis Thomas, MD is Not a Bore: The Life of a Biology Watcher (Steven Greenberg) Doctors from Hell: The Horrific Account of Nazi Experiments on Humans (Vivien Spitz) Illuminating Autism: Passing the Torch from the Twentieth Century (Student Essay Contest Winners) (Lynn Yudofsky) Healing Beyond Hippocrates: The Temples of Asclepius and Public Health Care in Ancient Greece (Andrew Baldwin) Iron Wills and Iron Lungs: The Polio Years in Texas (Heather Green Wooten) William Osler and the Inspirational Uses of History (Michael Bliss) Working Too Hard and Achieving Too Much: The Cost of Being Harvey Cushing (Michael Bliss) Medicine in Ancient Egypt (Gene Boisaubin) The History of Diabetes (Jeff Unger)

Houston History of Medicine Society 2008-2009 Schedule and Abstracts

The National Library of Medicine and the Continuing Legacy of Michael E. DeBakey, M.D. (Stephen B. Greenberg) The Legacy of William Osler: North America’s most famous physician (Robert E. Rakel) A Lady Alone: Elizabeth Blackwell: First American Woman Doctor (Linda Gray Kelley, Charlton) A Mariner with Crippling Arthritis and Bleeding Eyes: The Chronic Arthritis of Christopher Columbus (Frank C. Arnett) Generation C(affeine): A History of Caffeine Consumption and its Medical Implications (Student Essay Contest winners) (Priti Dangayach) Our Artificial Fitness? Relaxed Selection Leads to Medical Dependence (Student Essay Contest winners) Philip Boone Remembering John P. McGovern, M.D. (1921-2007) (Bryant Boutwell) Who Was Albert Schweitzer? (Bryant Boutwell) Disease, Doctors and the Duty to Treat in American History (Thomas R. Cole) Vaccinating Freedom: The African-American Experience of Smallpox Prophylaxis in Old Philadelphia, 1723-1923 (Dayle B. Delancey) The Royal Hemophilia (The Royal Hemophilia)