Evaluation of a web-based weight loss intervention in overweight cancer survivors aged 50 years and younger.

PURPOSE: Half of adult cancer survivors under age 50 years are obese. Excess body weight is associated with cancer recurrence, and effective weight loss interventions for younger cancer survivors are needed. Commercially available, online weight loss programmes are readily accessible, but few have been studied in this population. This study employed a single-arm, pre-post intervention (baseline-6 month/baseline-12 month comparisons) to preliminarily explore feasibility, efficacy and safety of an online, commercially available weight loss programme in breast (n = 30) and testicular (n = 16) cancer survivors under age 50 years. METHODS: The intervention included three daily components: exercise, nutritional/behavioural modification strategies and health lessons. Intention-to-treat and completers analyses were conducted. Feasibility was measured by participation (number of participants enrolled/number screened), retention (number of participants attending 6/12 month study visit/number of enrolled) and self-reported adherence rates (average of mean percent adherence to each of the three intervention components). Efficacy was assessed by changes in initial weight (percent weight loss). Safety was assessed by adverse events. RESULTS: The mean participation rate was 42%. The retention rate was 59% at 6 and 49% at 12 months. The adherence rate for all participants (completers/dropouts/lost-to-follow-up) was 50.1% at 6 and 44% at 12 months. Completers reported adherence rates of 68% at 12 months. Study participants lost 5.3% body weight at 12 months; completers lost 9%. Only three unexpected adverse events (unrelated to the intervention) were reported. CONCLUSION: Clinically significant weight loss was observed, although retention rates were low. Findings generally support preliminary feasibility, efficacy and safety of this online weight loss programme, and future randomized control trials should be explored.

Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer.

Experimental and clinical data support a role for estrogens in the development and growth of breast cancer, and lowered estrogen exposure reduces breast cancer recurrence and new diagnoses in high-risk women. There is varied evidence that increased physical activity is associated with breast cancer risk reduction in both pre- and postmenopausal women, perhaps via lowered estrogen levels. The purpose of this study was to assess whether exercise intervention in premenopausal women at increased breast cancer risk reduces estrogen or progesterone levels. Seven healthy premenopausal women at high risk for breast cancer completed a seven-menstrual-cycle study. The study began with two preintervention cycles of baseline measurement of hormone levels via daily first-morning urine collection, allowing calculation of average area under the curve (AUC) hormone exposure across the menstrual cycle. Participants then began five cycles of exercise training to a maintenance level of 300 min per week at 80-85% of maximal aerobic capacity. During the last two exercise cycles, urinary estradiol and progesterone levels were again measured daily. Total estrogen exposure declined by 18.9% and total progesterone exposure by 23.7%. The declines were mostly due to decreased luteal phase levels, although menstrual cycle and luteal phase lengths were unchanged. The study demonstrated the feasibility of daily urine samples and AUC measurement to assess hormone exposure in experimental studies of the impact of interventions on ovarian hormones. The results suggest value in exercise interventions to reduce hormone levels in high-risk women with few side effects and the potential for incremental benefits to surgical or pharmacologic interventions.

Impact of lymphedema and arm symptoms on quality of life in breast cancer survivors.

Lymphedema is one of many arm problems reported by breast cancer survivors. Understanding the impact of lymphedema on quality of life requires consideration that arm symptoms may occur with or without lymphedema. It was hypothesized that specific arm symptoms and pain, related or unrelated to lymphedema, would be more associated with quality of life outcomes than arm swelling. The relation of arm swelling and of arm symptoms and associated severity with a range of quality of life outcomes following breast cancer treatment was assessed in a diverse sample of 295 women, 141 of whom had a clinical diagnosis of lymphedema. Arm swelling (as defined by interlimb volume or circumference differences) and lymphedema severity (defined by Common Toxicity Criteria) were less correlated with quality of life than total number of arm symptoms and specific individual symptoms. Pain in the affected arm correlated with poor quality of life outcomes, regardless of arm swelling. When evaluating the impact of lymphedema on quality of life, arm swelling may not be as important as the total number and specific types of arm symptoms present, as these may be more informative about quality of life outcomes in survivors of breast cancer with and without lymphedema.

Comparison of the validity of anthropometric and bioelectric impedance equations to assess body composition in adolescent girls.

OBJECTIVE: The purpose of this study was to examine the validity of two anthropometric and four bioelectric impedance (BIA) equations to estimate body composition from dual-energy x-ray absorptiometry (DXA) in adolescent girls of various ethnicities. The rationale for this study was to develop a prediction equation for percent body fat in a multi-ethnic, representative sample of sixth to eighth grade girls. DESIGN: One-hundred and sixty-six girls (51 African-American, 45 non-Black Hispanic, 55 non-Hispanic Caucasian, 15 multi-ethnic) participated. Estimates of percent fat and fat-free mass (FFM) from six published BIA and anthropometric equations and the equation developed from this study were compared to body composition determined from DXA. An RJL Systems analyzer was used to measure BIA. Anthropometry included body weight, height, and triceps and calf skinfolds. RESULTS: Average (± SD) age, size and body composition was as follows: age, 12.1±1.2 yrs, body mass 52.7±15.9 kg, height, 154.6±8.1 cm; DXA percent fat, 27.9±10.4; fat mass (FM), 15.6±10.2 kg; and fat free mass (FFM) 35.7±6.8 kg. No ethnic differences were found in the relationships between estimated and DXA measured body composition, with the exception of the skinfold equation. The six equations explained on average 82% of the variance in percent fat, 94% of the variance in fat mass, and 88% in fat free mass. Bland-Altman analysis indicated that none of the equations performed satisfactorily in our sample. CONCLUSIONS: The BIA and anthropometric equations were significantly related to DXA body composition parameters, however none met the criteria for cross-validation.

Changes in inflammatory biomarkers following one-year of moderate resistance training in overweight women.

BACKGROUND: Overweight individuals commonly demonstrate elevated levels of inflammatory and cell adhesion molecules. Elevated levels of inflammation and adhesion have been implicated in the pathogenesis of cardiovascular disease. Aerobic exercise has been shown to be effective in altering specific biomarkers of inflammation and cell adhesion; however, little is known regarding the effects of resistance training (RT) on these biomarkers. This study examined the effects of 1 year of moderate-intensity RT on biomarkers of inflammation and adhesion in healthy, overweight women. METHODS AND RESULTS: Participants included 28 (12 control, 16 RT) overweight (body mass index>or=25 kg/m2) women, aged 25-44 years, studied before and after 1 year of RT. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, intracellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin were measured by standard enzyme-linked immunosorbent assays. Body composition, blood pressure, fasting blood lipids, glucose and insulin also were assessed. There were no significant changes in blood pressure, fasting blood lipids, glucose or insulin levels in either group after 1 year. There was also no change in body mass or fat mass in either group; however, there was a significant increase in lean body mass (P<0.05) in the RT group. Both CRP (P<0.01) and adiponectin (P<0.01) demonstrated significant improvements in the RT group, with no change in IL-6. Conversely, there were no associated changes in the biomarkers of cell adhesion in either group. CONCLUSIONS: This study demonstrates that moderate-intensity RT significantly results in modest improvements of inflammatory markers without affecting cell adhesion molecules in overweight women.

Anastomotic stenting in a porcine aortoiliac graft model.

The purpose of the study was to evaluate the feasibility of anastomotic stent application in a porcine aortoiliac graft model. In a total of 10 pigs, a polytetrafluoroethylene aortobi-iliac graft was implanted through a midline abdominal incision. The lower edge of the iliac vessel was graft-inverted about 1 mm to produce irregularities at the downstream anastomosis. After transverse graft incision, six stainless-steel stents, six poly-L-lactic acid (PLLA) stents and four PLLA stents with 10% polycaprolactone (PCL) were implanted at the iliac anastomotic site using a 6 mm balloon dilatation catheter. Four anastomotic sites were left untreated. After two weeks, the patency of graft limbs was evaluated by contrast-enhanced computed tomography (CT). Both metal and polymeric stent designs provided adequate flexibility to manoeuvre across the anastomotic site for expansion in the chosen position. After deployment, the stent-arterial wall contact was complete on a macroscopic view. On CT scan, all metal and PLLA-stented graft limbs were free of stenosis, whereas all PLLA/PCL stents were occluded. The non-stented graft limbs showed a stenosis of 50-70%. In summary, this model is feasible to assess preclinically the deployment and patency rate of an anastomotic stent and to test future stent developments.

Strength training for obesity prevention in midlife women.

OBJECTIVE: The primary goal of this study was to assess whether increases in fat-free mass (FFM) and decreases in total and percentage fat mass from 15 weeks of twice weekly supervised strength training would be maintained over 6 months of unsupervised exercise in a randomized controlled trial. DESIGN: In all, 60 women aged 30-50 y, body mass index between 20 and 35 kg/m(2), were randomized to control or treatment groups. The treatment group performed twice-weekly supervised strength training followed by 6 months of unsupervised training. Measurements at baseline, 15, and 39 weeks included body weight and body composition by dual-energy X-ray absorptiometry. Repeated measures regression was used to assess between-group differences for changes over time. RESULTS: Almost 90% of prescribed exercise sessions were completed. The body composition treatment effects over 15 weeks were largely maintained over 6 months of unsupervised exercise. Over the total 39 weeks of strength training, the treatment group gained +0.89 kg more in FFM, lost -0.98 kg more in fat mass, and lost -1.63% more in percent body fat when compared to the control group. P-values for these between-group differences in 39-week changes were 0.009, 0.06, and 0.006, respectively. Strength training did not result in any significant weight loss or waist circumference attenuation. Adjustment for changes in energy intake and physical activity did not alter these results. CONCLUSIONS: Twice-weekly strength training is behaviorally feasible for busy midlife women and the favorable body composition changes resulting from supervised strength training can be maintained over time. These findings lay the groundwork for determining the long-term health benefits of this behaviorally feasible exercise prescription, potentially including prevention of age-associated fat gains.

Association of physical activity with insulin sensitivity in children.

BACKGROUND: Physical activity (PA) has been shown to improve insulin resistance and other cardiovascular disease risk factors in normal and diabetic adults and in obese youth, but not in non-diabetic, normal-weight children. METHODS: Data from 357 non-diabetic children (10-16 y) were used to examine cross-sectional associations with PA. Insulin sensitivity was assessed with a euglycemic hyperinsulinemic clamp and expressed as M(ffm) (glucose utilization/kg of fat-free mass/min). RESULTS: Correlations were adjusted for age, sex, race and Tanner stage. PA was significantly correlated with fasting insulin and insulin sensitivity (r=-0.12, P=0.03 and r=0.13, P=0.001, respectively), more strongly in children with above-median systolic blood pressure (r=-0.17, P=0.03 and r=0.35, P=0.0001, respectively). Further adjustment for body mass index, body fat percentage, waist circumference or lipids did not alter these observations. CONCLUSIONS: Physical activity is correlated with lower fasting insulin and greater insulin sensitivity in childhood. These results are consistent with the hypothesis that increasing physical activity among youth may reduce the incidence of type 2 diabetes in children and adolescents.

Arterial distensibility and physical activity in the ARIC study.

PURPOSE: Arterial distensibility decreases with age. This decrease may be associated with the initiation and/or progression of hypertension and atherosclerosis and may be attenuated by positive lifestyle habits, including habitual physical activity. We tested the hypothesis that self-reported sport, leisure, and work physical activity is associated with greater arterial distensibility (i.e., carotid artery pulsatile diameter changes). METHODS: The Atherosclerosis Risk in Communities (ARIC) study assessed left common carotid arterial diameters and intimal-medial wall thickness (IMT) using B-mode ultrasound techniques, in 10,644 African-American and white men and women aged 45-64 yr and free of cardiovascular disease. RESULTS: Work activity, but not sports or leisure activity, was weakly associated with greater arterial distensibility in an ANCOVA model adjusted for blood pressure and other covariates (diastolic arterial diameter, pulse pressure, pulse pressure squared, age, race, sex, smoking, dietary fat intake, height, education, and clinical center) (P for linear trend = 0.03). Vigorous sports activity was weakly positively associated with arterial distensibility (arterial diameter change (mean +/- SE in mm) 0.42 +/- 0.004 vs 0.41 +/- 0.002 for the 12.7% of participants reporting any vs no vigorous activity, P = 0.02), and this association was not attenuated by adjustment for IMT, body mass index, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or diabetes. Repeated analyses with traditional arterial stiffness indices showed similar findings for vigorous but not work activity. CONCLUSION: In contrast to several smaller studies, these findings do not support the hypothesis that habitual physical activity has a strong, consistent positive effect on arterial distensibility.

Independent and interactive effects of apolipoprotein E phenotype and cardiorespiratory fitness on plasma lipids.

PURPOSE: To examine whether the association Apolipoprotein E (Apo E) phenotype with plasma lipids is influenced by physical fitness level. Also, to explore the interactive and independent relative contributions of Apo E phenotype, fitness (or physical activity), and other modifiable factors to variation in plasma low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) levels at baseline and over a seven-year follow-up. METHODS: Physical fitness (duration of a graded treadmill test), Apo E phenotype, plasma LDL-C and HDL-C, and covariates were measured at baseline and seven years later in a bi-racial cohort of young adults, aged 18-30 years at baseline in 1985-86, from the Coronary Artery Risk Development In Young Adults (CARDIA) study. RESULTS: Fitness did not influence the associations of Apo E and LDL-C or HDL-C. The independent effects of several modifiable variables (changes in Keys' score, smoking, oral contraceptive use, education, body weight, alcohol intake, and fitness), when combined, contributed considerably more than Apo E to the variance in LDL-C changes (6.74% or 8.71% for combined modifiable variables vs. 1.27% or 0.90% for ApoE, in women or men, respectively) and HDL-C changes (13.11% or 12.66% for combined modifiable variables vs. 0.12% or 0.02% for ApoE, in women or men, respectively). The pattern of findings was similar when self-reported physical activity was substituted for fitness. CONCLUSIONS: Changes in modifiable factors, including fitness, may be stronger correlates of changes in LDL-C and HDL-C over time than the immutable factor, Apo E phenotype.

Compendium of physical activities: an update of activity codes and MET intensities.

We provide an updated version of the Compendium of Physical Activities, a coding scheme that classifies specific physical activity (PA) by rate of energy expenditure. It was developed to enhance the comparability of results across studies using self-reports of PA. The Compendium coding scheme links a five-digit code that describes physical activities by major headings (e.g., occupation, transportation, etc.) and specific activities within each major heading with its intensity, defined as the ratio of work metabolic rate to a standard resting metabolic rate (MET). Energy expenditure in MET-minutes, MET-hours, kcal, or kcal per kilogram body weight can be estimated for specific activities by type or MET intensity. Additions to the Compendium were obtained from studies describing daily PA patterns of adults and studies measuring the energy cost of specific physical activities in field settings. The updated version includes two new major headings of volunteer and religious activities, extends the number of specific activities from 477 to 605, and provides updated MET intensity levels for selected activities.

Physical activity and body weight: associations over ten years in the CARDIA study. Coronary Artery Risk Development in Young Adults.

BACKGROUND: Hypothesis 1--sustained changes in physical activity are inversely related to changes in body weight. Hypothesis 2-those who attenuate weight gain because of a temporary increase in physical activity (PA) may maintain a lower body weight over time. METHODS: Data were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a cohort of black and white men and women, aged 18-30y at baseline, who attended up to five examinations over a 10y period (n=5,115 at baseline). Longitudinal associations between physical activity and body weight changes were assessed, adjusting for secular trend, age, clinic site, education, smoking, alcohol intake, parity, percentage energy intake from fat, and changes in these variables over time. For hypothesis 1, concurrent associations of physical activity and body weight changes were examined. For hypothesis 2, we explored whether weight gain attenuation associated with increased PA during the initial 2-3 y of follow-up was sustained over 5 y. The study 2 analyses were conducted with three separate 5y intervals: baseline to year 5 (n= 3,641), years 2-7 (n= 3,160), and years 5-10 (n= 2,617). RESULTS: Hypothesis 1 -change in physical activity was inversely associated with change in body weight within all four race and sex sub-groups (P<0.005). The predicted weight change associated with change in physical activity was four to five times larger in participants who were overweight compared with those who were not were overweight at baseline. Hypothesis 2-an increase in physical activity during 2-3 y of follow-up was associated with an attenuation of weight gain that was sustained through 5y of follow-up whether or not the physical activity increase was maintained during the later years. This finding persisted whether the starting point for the 5y follow-up was year 2, year 5 or baseline (women only). Comparing participants who increased physical activity with those who decreased physical activity in the first 2-3 y of follow-up (eg by at least 2 h per week of stationary cycling for at least 6 months per year), the mean 5y weight gain attenuation ranged from 0.8 to 2.8 kg. CONCLUSIONS: The results of these analyses support the need for public health messages for promoting increased physical activity for weight maintenance and attenuation of age-related weight gain, especially for higher weight sub-populations.

Effects of recombinant human tumor necrosis factor on rodent gliomas and normal brain.

In a study examining the possible therapeutic effects of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) on malignant gliomas without expression of tumor necrosis factor (TNF)-receptors, RG-2 glioma cells were tested in vitro as well as in a rat experimental glioma model. A growth inhibition assay revealed no inhibiting effect in vitro up to a concentration of 20 micrograms/ml rHuTNF-alpha. Receptor-binding studies showed that RG-2 cells did not present specific receptors for rHuTNF-alpha. The pharmacokinetics of rHuTNF-alpha after intravenous injection were studied with respect to serum, tissue, and brain tumor concentrations and showed increased glioma concentrations of (mean +/- standard error of the mean) 0.47 +/- 0.18 ng TNF/mg brain compared to 0.15 +/- 0.05 ng TNF/mg brain in the normal contralateral hemisphere. No therapeutic effect on solid RG-2 gliomas could be observed after stereotactic injection of 7.3 micrograms rHuTNF/10 microliter buffer solution into the tumor in 10 animals. Immunohistochemical studies after stereotactic injection of rHuTNF-alpha showed total disappearance of the substance after 24 hours without internalization into tumor cells. Stereotactic injection of 7.3 micrograms rHuTNF 10 microliters into normal brain resulted in marked inflammatory response around the injection track, including microvascular thrombosis. These results demonstrate that rHuTNF has neither direct nor indirect cytotoxic activity on RG-2 glioma cells. Furthermore, before clinical use of rHuTNF-alpha in malignant gliomas, the authors suggest that receptor studies be done in each patient. In receptor-positive patients undergoing treatment with rHuTNF-alpha, precautions should be taken to prevent local encephalitic reactions.