J. N. Udall

The health benefits of physical activity in children and adolescents : implications for chronic disease prevention

Abstract Clinical, epidemiological and basic research evidence clearly supports the inclusion of regular physical activity as a tool for the prevention of chronic disease and the enhancement of overall health. In children, activities of a moderate intensity may enhance overall health, and assist in preventing chronic disease in at-risk youth. The numerous health benefits of regular exercise are dependent on the type, intensity and volume of activity pursued by the individual. These benefits include reduction of low density lipoproteins while increasing high density lipoprotein; improvement of glucose metabolism in patients with type II diabetes; improved strength, self esteem and body image; and reduction in the occurrence of back injuries. In addition, a progressive, moderate-intensity exercise program will not adversely effect the immune system and may have a beneficial effect on the interleukin-2/natural killer cell system. Furthermore, by decreasing sedentary behaviors and, thus, increasing daily physical activity, individuals may experience many stress-reducing benefits, which may enhance the immune system. Conclusion Moderate intensity exercise of a non-structured nature seems to facilitate most of the disease prevention goals and health promoting benefits. With new guidelines promoting a less intense and more time-efficient approach to regular physical activity, it is hoped that an upward trend in the physical activity patterns, and specifically children at risk for chronic disease, will develop in the near future.

Exonic and Intronic Sequence Variation in the Human Leptin Receptor Gene (LEPR)

Increased adiposity is a major risk factor for cardiovascular disease and NIDDM (1). Genetic determinants of the degree of adiposity and body fat distribution have been demonstrated by twin and adoption studies, and the heritability (h) of obesity has been estimated to be as high as 0.90 (2). However, the major genes underlying the heritable contribution to body fatness in humans have remained elusive. Rodent models of genetically determined obesity provide excellent candidate genes for evaluation in humans. The linkage of obesity-related phenotypes in humans to genomic regions homologous to rodent leptin (Lep) (3) and leptin receptor (Lepr) (4,5) has been recently demonstrated. The recent cloning of Lepr, which is mutant in the diabetes (Lepr^) mouse and in fatty (Lepr) and Koletsky (Lepr) rats (6-9), the mapping of this gene (LEPR) to Ip32 in humans (10), and the description of the genomic structure of LEPR and two polymorphic intronic microsatellites (11) have provided the necessary reagents for the evaluation of LEPR in the genetics of human obesity. Because the phenotype associated with genetic defects in Lepr in Lepr/Lepr mice and Lepr/Lepr rats is profound early-onset obesity, we sought to identify allelic variations in LEPR, which may be responsible for the genetic variation in adiposity in humans. To maximize the likelihood of the detection of such sequence variants, we examined genomic DNA from a total of 229 obese and lean adults and children, ascertained in medical centers around the U.S. (New York, New York; New Orleans, Louisiana; and Huntington, West Virginia). The study sample was predominantly Caucasian, but also

Safety, Feasibility, and Efficacy of a Resistance Training Program In Preadolescent Obese Children

BACKGROUND Safe and effective exercise programs are needed to prevent and treat chronic diseases in childhood. In particular, preadolescent obese children should participate in activities that are specific to their special needs. Resistance or strength training has been prescribed for adult obese persons. Research is limited concerning the use of resistance training in programs that treat obese preadolescents. METHODS Nineteen treatment subjects (7-12 years of age) were enrolled in a 10-week weight management program which included diet, behavior modification, and aerobic and flexibility exercises. Forty-eight control subjects (7-12 years of age) participated in the diet, behavior modification program, and a thrice-a-week walking program. The efficacy of the overall weight management program was examined by anthropometry at 10 weeks and 1 year. RESULTS Fifteen treatment subjects completed the 10-week program (retention rate, 78.9%). Thereafter compliance decreased by approximately 33% for the long-term study. Seventeen control subjects completed the program (retention rate, 35%). Weight, percent of ideal body weight, and body mass index were reduced significantly at 10 weeks (P<0.0001) and did not increase significantly at 1-year follow-up in both treatment and control groups. Height increased significantly at 1 year in both treatment and control subjects. In the treatment subjects, percent fat decreased significantly (P<0.001), whereas fat-free mass did not change significantly (P>0.05). CONCLUSIONS A resistance-training program may be included safely in a multidisciplinary weight management program for obese preadolescent male and female children. The addition of specific exercise regimes such as resistance training may improve program retention especially in severely obese youth.

Use of Infliximab in Pediatric Patients with Inflammatory Bowel Disease

BACKGROUND: The concentration of tumor necrosis factor, a proinflammatory cytokine, is increased in the gastrointestinal mucosa of patients with active Crohns disease (CD) and ulcerative colitis (UC). Neutralization of tumor necrosis factor decreases the mucosal inflammatory response of adults with CD. Little information is available on the use of monoclonal antibody to tumor necrosis factor (infliximab) in children and adolescents with CD or UC. OBJECTIVE: To evaluate the clinical response and side effects of patients to infliximab. METHODS: A retrospective review of data regarding 18 pediatric and adolescent patients with active CD (n = 15) and UC (n = 3) poorly controlled with conventional therapy. All patients received one to six intravenous infusions of infliximab 5 mg/kg, while receiving their usual medications. RESULTS: All patients experienced clinical improvement, including decrease in the frequency of stooling and resolution of extraintestinal symptoms such as arthropathy, malaise, and skin manifestations after treatment with infliximab. All but one patient had a documented decrease in the erythrocyte sedimentation rate. Prednisone dosage was tapered in all but two patients, and discontinued in seven patients. Intravenous infusion of infliximab was well tolerated. One patient developed a rash several days after the infusion. A patient who received six infliximab infusions developed recurrent Staphylococcus aureus infections, as well as septic arthritis and chronic osteomyelitis during the follow-up period, raising the issue of the long-term safety of infliximab. CONCLUSIONS: Treatment of our patients with refractory CD and UC with infliximab was associated with remarkable clinical improvement. Although the drug may have an important role in their management, further assessment of long-term safety and efficacy is needed.

Weight loss and growth velocity in obese children after very low calorie diet, exercise, and behavior modification

The prevalence of obesity in American youth is increasing and treatment of the condition is difficult. We have developed a multi‐disciplinary weight reduction program that extends over 1 y and includes a very low‐calorie diet (VLCD) followed by a hypocaloric diet, exercise, and behavior modification. Based on data collected at baseline, at the end of the acute intervention phase (10–20 wk), and at 1‐y evaluation, we assessed the efficacy of this outpatient weight reduction program in treating obese children and adolescents in a follow‐up of a series of cases. Furthermore, we examined the impact of the approach on growth velocity and maintenance of weight loss at 1 y. Fifty‐six overweight children (aged 7–17 y) were recruited during a period of 18 mo to participate in the weight management program; 52 (93%) completed the acute phase of treatment and 35 (62.5%) successfully completed the I‐y program. There was a significant decrease in body weight and body fat, as assessed by weight determinations and skinfold measurements 0, < 0.0001; results not corrected for age). The body mass index for the 35 individuals who completed the 1‐y program decreased significantly from 32.7 on entry to 28.72 at 1 y (p < 0.0001; results not corrected for age).

Effect of Obesity Status on Heart Rate Peak in Female Youth

The purpose of this study was to compare heart rate peak in obese (n=43) and normal weight (n=45) female youth. Heart rate (HR) peak was significantly lower (p<0.05) in the obese group as compared to the normal weight group (192.3±29.3, 203.4±27.6), and V02 (L min-) peak similar between groups (1.77±20.53, 1.97±0.60). Bivariate correlations for heart rate peak with body weight, percent fat, and body mass index yielded the following: -0.53, -0.54, and -0.57. These findings agree with the adult data indicating low HR peak in obese individuals. Further research is needed to explore physiologic factors that may lead to reduced HR peak in obese female youth.

Association of the T allele of an intronic single nucleotide polymorphism in the colony stimulating factor 1 receptor with Crohn's disease: a case-control study

BackgroundPolymorphisms in several genes (NOD2, MDR1, SLC22A4) have been associated with susceptibility to Crohns disease. Identification of the remaining Crohns susceptibility genes is essential for the development of disease-specific targets for immunotherapy. Using gene expression analysis, we identified a differentially expressed gene on 5q33, the colony stimulating factor 1 receptor (CSF1R) gene, and hypothesized that it is a Crohns susceptibility gene. The CSF1R gene is involved in monocyte to macrophage differentiation and in innate immunity.MethodsPatients provided informed consent prior to entry into the study as approved by the Institutional Review Board at LSU Health Sciences Center. We performed forward and reverse sequencing of genomic DNA from 111 unrelated patients with Crohns disease and 108 controls. We also stained paraffin-embedded, ileal and colonic tissue sections from patients with Crohns disease and controls with a polyclonal antibody raised against the human CSF1R protein.ResultsA single nucleotide polymorphism (A2033T) near a Runx1 binding site in the eleventh intron of the colony stimulating factor 1 receptor was identified. The T allele of this single nucleotide polymorphism occurred in 27% of patients with Crohns disease but in only 13% of controls (X2 = 6.74, p < 0.01, odds ratio (O.R.) = 2.49, 1.23 < O.R. < 5.01). Using immunohistochemistry, positive staining with a polyclonal antibody to CSF1R was observed in the superficial epithelium of ileal and colonic tissue sections.ConclusionsWe conclude that the colony stimulating factor receptor 1 gene may be a susceptibility gene for Crohns disease.