James E. Norman

Defining Accelerometer Thresholds for Activity Intensities in Adolescent Girls

Implications for Muscle Lipid Metabolism and An accumulation of intramuscular lipid has been reported with obesity and linked with insulin resistance. The purpose of this paper is to discuss: 1) mechanisms that may be responsible for intramuscular lipid accumulation with obesity, and 2) the effects of common interventions (weight loss or exercise) for obesity on skeletal muscle lipid metabolism and intramuscular lipid content. Data suggest that the skeletal muscle of morbidly obese humans is characterized by the preferential partitioning of lipid toward storage rather than oxidation. This phenotype may, in part, contribute to increased lipid deposition in both muscle and adipose tissue, and promote the development of morbid obesity and insulin resistance. Weight loss intervention decreases intramuscular lipid content, which may contribute to improved insulin action. On the other hand, exercise training improves insulin action and increases fatty acid oxidation in the skeletal muscle of obese/morbidly obese individuals. In summary, the accumulation of intramuscular lipid appears to be detrimental in terms of inducing insulin resistance; however, the accumulation of lipid can be reversed with weight loss. The mechanism(s) by which exercise enhances insulin action remains to be determined.INTRODUCTION/PURPOSE The Talk Test has been shown to be well correlated with the ventilatory threshold, with accepted guidelines for exercise prescription, and with the ischemic threshold. As such, it appears to be a valuable although quite simple method of exercise prescription. In this study, we evaluate the consistency of the Talk Test by comparing responses during different modes of exercise. METHODS Healthy volunteers (N = 16) performed incremental exercise, on both treadmill and cycle ergometer. Trials were performed with respiratory gas exchange and while performing the Talk Test. Comparisons were made regarding the correspondence of the last positive, equivocal, and first negative stages of the Talk Test with ventilatory threshold. RESULTS The %VO2peak, %VO2 reserve, %HRpeak, and %HR reserve at ventilatory threshold on treadmill versus cycle ergometer (77%, 75%. 89%, and 84% vs 67%, 64%, 82%, and 74%) were not significantly different than the equivocal stage of the Talk Test (83%, 82%, 86%, and 80% vs 73%, 70%, 87%, and 81%). The VO2 at ventilatory threshold and the last positive, equivocal and negative stages of the Talk Test were well correlated during treadmill and cycle ergometer exercise. CONCLUSIONS The results support the hypothesis that the Talk Test approximates ventilatory threshold on both treadmill and cycle. At the point where speech first became difficult, exercise intensity was almost exactly equivalent to ventilatory threshold. When speech was not comfortable, exercise intensity was consistently above ventilatory threshold. These results suggest that the Talk Test may be a highly consistent method of exercise prescription.INTRODUCTION Obesity and weight gain are negative prognostic factors for breast cancer survival. Physical activity (PA) prevents weight gain and may decrease obesity. Little information exists on PA levels among cancer survivors. We assessed PA, including the proportion of breast cancer survivors engaging in recommended levels, by categories of adiposity, age, disease stage, and ethnicity in 806 women with stage 0-IIIA breast cancer participating in the Health, Eating, Activity, and Lifestyle Study. METHODS Black, non-Hispanic white, and Hispanic breast cancer survivors were recruited into the study through Surveillance Epidemiology End Results registries in New Mexico, Western Washington, and Los Angeles County, CA. Types of sports and household activities and their frequency and duration within the third yr after diagnosis were assessed during an in-person interview. RESULTS Thirty-two percent of breast cancer survivors participated in recommended levels of PA defined as 150 min x wk(-1) of moderate- to vigorous-intensity sports/recreational PA. When moderate-intensity household and gardening activities were included in the definition, 73% met the recommended level of PA. Fewer obese breast cancer survivors met the recommendation than overweight and lean breast cancer survivors (P < 0.05). Fewer black breast cancer survivors met the recommendation compared with non-Hispanic white and Hispanic breast cancer survivors (P < 0.05). CONCLUSIONS Most of the breast cancer survivors were not meeting the PA recommendations proposed for the general adult population. Efforts to encourage and facilitate PA among these women would be an important tool to decrease obesity, prevent postdiagnosis weight gain, and improve breast cancer prognosis.PURPOSE To derive a regression equation that estimates metabolic equivalent (MET) from accelerometer counts, and to define thresholds of accelerometer counts that can be used to delineate sedentary, light, moderate, and vigorous activity in adolescent girls. METHODS Seventy-four healthy 8th grade girls, age 13 - 14 yr, were recruited from urban areas of Baltimore, MD, Minneapolis/St. Paul, MN, and Columbia, SC, to participate in the study. Accelerometer and oxygen consumption (.-)VO(2)) data for 10 activities that varied in intensity from sedentary (e.g., TV watching) to vigorous (e.g., running) were collected. While performing these activities, the girls wore two accelerometers, a heart rate monitor and a Cosmed K4b2 portable metabolic unit for measurement of (.-)VO(2). A random-coefficients model was used to estimate the relationship between accelerometer counts and (.-)VO(2). Activity thresholds were defined by minimizing the false positive and false negative classifications. RESULTS The activities provided a wide range in (.-)VO(2) (3 - 36 mL x kg x min) with a correspondingly wide range in accelerometer counts (1- 3928 counts x 30 s). The regression line for MET score versus counts was MET = 2.01 +/- 0.00171 (counts x 30 s) (mixed model R = 0.84, SEE = 1.36). A threshold of 1500 counts x 30 s defined the lower end of the moderate intensity (approximately 4.6 METs) range of physical activity. That cutpoint distinguished between slow and brisk walking, and gave the lowest number of false positive and false negative classifications. The threshold ranges for sedentary, light, moderate, and vigorous physical activity were found to be 0 - 50, 51- 1499, 1500 - 2600, and >2600 counts x 30 s, respectively. CONCLUSION The developed equation and these activity thresholds can be used for prediction of MET score from accelerometer counts and participation in various intensities of physical activity in adolescent girls.

Diuretic use, progressive heart failure, and death in patients in the studies of left ventricular dysfunction (SOLVD)

OBJECTIVES We sought to determine whether non-potassium-sparing diuretics (PSDs) in the absence of a PSD may result in progressive heart failure (HF). BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors incompletely suppress ACE activity in HF patients. Furthermore, non-PSDs are activators of aldosterone secretion. We reasoned that non-PSDs, in the absence of a PSD, might result in progressive HF. METHODS In the 6,797 patients in the Studies Of Left Ventricular Dysfunction (SOLVD), we compared the risk of hospitalization for, or death from, HF between those taking a PSD and those who were not, adjusting for known covariates. RESULTS The risk of hospitalization from worsening HF in those taking a PSD relative to those taking only a non-PSD was 0.74 (95% confidence interval [CI] 0.55 to 0.99; p = 0.047). The relative risk for cardiovascular death was 0.74 (95% CI 0.59 to 0.93; p = 0.011), for death from all causes 0.73 (95% CI 0.59 to 0.90; p = 0.004), and for hospitalization for, or death from, HF 0.75 (95% CI 0.58 to 0.97; p = 0.030). Compared with patients not taking any diuretic, the risk of hospitalization or death due to worsening HF in patients taking non-PSDs alone was significantly increased (risk ratio [RR] = 1.31, 95% CI 1.09 to 1.57; p = 0.0004); this was not observed in patients taking PSDs with or without a non-PSD (RR = 0.99, 95% CI 0.76 to 1.30; p = 0.95). CONCLUSIONS The use of PSDs in HF patients is associated with a reduced risk of death from, or hospitalization for, progressive HF or all-cause or cardiovascular death, compared with patients taking only a non-PSD.

Effects of total pathogen burden on coronary artery disease risk and C-reactive protein levels

Infection and inflammation have been suggested to play roles in coronary artery disease (CAD). We hypothesized that: (1) CAD risk is associated with the aggregate number of pathogens (pathogen burden), and (2) increased pathogen burden is associated with elevated levels of C-reactive protein (CRP), a marker of inflammation. We evaluated 233 patients for CAD. Blood samples from each patient were tested for immunoglobulin-G (IgG) antibodies to cytomegalovirus (CMV), Chlamydia pneumoniae, hepatitis A virus (HAV), herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2), and for the CRP levels. Of the 233 study subjects, 68% had evidence of CAD by coronary angiography. Although the prevalence of seropositivity for each pathogen tended to be higher in the patients with CAD than those without, only the association between CAD and seropositivity to HAV was significant in multivariate analysis. Over 75% of study subjects had been exposed to > or =3 of the 5 pathogens tested, and analysis determined that increasing pathogen burden was significantly associated with increasing CAD risk, even after adjustment for traditional CAD risk factors. The prevalence of CAD was 48%, 69%, and 85% in individuals with antibodies to < or =2 pathogens, to 3 or 4 pathogens, and to 5 pathogens, respectively. A similar association between increasing pathogen burden and CRP levels was also found. The pathogen burden remained a significant predictor of CRP levels after multivariate analysis. Our data suggest that infection does play a role in the genesis of atherosclerosis. However, the risk posed by infection is related to the pathogen burden that may contribute to CAD through inflammatory responses.

Epidemiology of multiple sclerosis in U.S. veterans 1. Race, sex, and geographic distribution

Five thousand three hundred five World War II and Korean conflict veterans who have been compensated by the Veterans Administration for multiple sclerosis (MS) were matched to controls on the basis of age, date of entry into military service, and branch of service. Case/control ratios for white males, white females, and black males were 1.04, 1.86, and 0.45, respectively. The coterminous 48 states, divided into three tiers on the basis of latitude, exhibited the well-known north-south gradient in risk: For all races and both sexes, case/control ratios were 1.41, 1.00, and 0.53 for the North, Middle, and South tiers. Both white females and black males showed this same north-to-south variation in risk. The case/control ratio for males of races other than black or white was 0.23, with possible deficits in risk for American Indians and Japanese-Americans. Filipinos and Hawaiian Japanese were significantly low-risk groups. These findings suggest that both a racial and a possibly genetic predisposition, as well as a geographically determined differential exposure to an environmental agent, are related to the risk of MS.

Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction

OBJECTIVES The purpose of this study was to evaluate the relationship of baseline pulse pressure and mean arterial pressure to mortality in patients with left ventricular dysfunction. BACKGROUND Increased conduit vessel stiffness increases pulse pressure and pulsatile load, potentially contributing to adverse outcomes in patients with left ventricular dysfunction. METHODS Pulse and mean arterial pressure were analyzed for their effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 6,781 patients randomized into the Studies of Left Ventricular Dysfunction trials. RESULTS Pulse and mean arterial pressure were related positively to each other, age, ejection fraction and prevalence of diabetes and hypertension and inversely to prior myocardial infarction and beta-adrenergic blocking agent use. Higher pulse pressure was associated with increased prevalence of female gender, greater calcium channel blocking agent, digoxin and diuretic use, lower heart rate and a higher rate of reported smoking history. Higher mean arterial pressure was associated with higher heart rate, lower calcium channel blocker and digoxin use and lower New York Heart Association functional class. Over a 61-month follow-up 1,582 deaths (1,397 cardiovascular) occurred. In a multivariate analysis adjusting for the above covariates and treatment assignment, higher pulse pressure remained an independent predictor of total and cardiovascular mortality (total mortality relative risk, 1.05 per 10 mm Hg increment; 95% confidence interval, 1.01 to 1.10; p = 0.02). Mean arterial pressure was inversely related to total and cardiovascular mortality (total mortality relative risk, 0.89; 95% confidence interval, 0.85 to 0.94; p <0.0001). CONCLUSIONS One noninvasive blood pressure measurement provides two independent prognostic factors for survival. Increased conduit vessel stiffness, as assessed by pulse pressure, may contribute to increased mortality in patients with left ventricular dysfunction, independent of mean arterial pressure.

A serologic follow-up of the 1942 epidemic of post-vaccination hepatitis in the United States Army

An epidemic of icteric hepatitis in 1942 affected approximately 50,000 U.S. Army personnel. This outbreak was linked to specific lots of yellow-fever vaccine stabilized with human serum. To identify the responsible virus and the consequences of the epidemic, during 1985 we interviewed and serologically screened 597 veterans who had been in the army in 1942. These subjects were selected from three groups. Group I consisted of patients who had received the implicated vaccine and had jaundice; Group II had received the implicated vaccine but remained well; Group III had received a new, serum-free vaccine, with no subsequent jaundice. Ninety-seven percent of Group I, 76 percent of Group II, and 13 percent of Group III were positive for antibodies to hepatitis B virus. Only one subject had hepatitis B surface antigen, for a carrier rate of 0.26 percent among recipients of the implicated vaccine. The prevalence of hepatitis A antibody was similar in all three groups, and no subject had antibody to hepatitis delta virus. We conclude that hepatitis B caused the outbreak, that about 330,000 persons may have been infected, that the hepatitis B virus carrier state was a rare consequence, and that the outbreak induced hepatitis B antibodies that appear to persist for life.

Cytomegalovirus in the pathogenesis of atherosclerosis: the role of inflammation as reflected by elevated C-reactive protein levels.

OBJECTIVES We hypothesized that cytomegalovirus (CMV) infection: 1) stimulates an inflammatory response, reflected by elevated C-reactive protein (CRP) levels, and 2) predisposes to coronary artery disease (CAD), in part, through CMV-induced inflammation. BACKGROUND Although some studies show an association between CMV and atherosclerosis, others do not. We believed that CMV exerted an atherogenic effect by inducing inflammation, and the disparate results may derive partly from individual variability in the capacity to control CMV inflammatory activity. METHODS Blood samples were tested for CMV seropositivity and CRP levels from 238 individuals being evaluated for CAD by coronary angiography. RESULTS An elevated CRP level (>0.5 mg/dl) was a significant CAD determinant even after adjustment for traditional CAD risk factors (odds ratio [OR] = 2.4; p = 0.02). Moreover, CMV seropositivity was significantly associated with increased CRP levels (p = 0.04 after adjustment for CAD risk factors), suggesting that CMV could evoke a subclinical inflammatory response. However, considerable host variation existed in this response to CMV. When adjusted for CAD risk factors, the OR for CAD were 1.3 in the subgroup with CMV seropositivity alone (p = 0.7), 2.3 in the subgroup with elevated CRP levels alone (p = 0.2), and 4.3 in the subgroup with combined CMV seropositivity and elevated CRP levels (p = 0.01). CONCLUSIONS Our results suggest that 1) CMV elicits a subclinical inflammatory response, but only in certain individuals, and 2) individuals with an inflammatory response appear susceptible to the atherogenic effects of CMV, whereas those without appear resistant. These results may partly explain the disparate results of studies attempting to relate CMV to atherogenesis.

Epidemiology of Multiple Sclerosis in US Veterans

Previously, we studied the effect of population ancestry on the risk of multiple sclerosis (MS) in US veterans of World War II, comparing by state 1980 US census ancestry data with MS case/control rat

Epidemiology of multiple sclerosis in US veterans III. Migration and the risk of MIS

World War II or Korean Conflict veterans with MS (5,305 in number) and pre-illness-matched controls were compared for residence at birth and entry on active duty (EAD) within three north-south tiers of states in the United States. A strong north-south gradient of MS risk was present. Migrants were defined as those whose birth and EAD tier differed. For white men of World War II, all white men, and all whites, there were highly significant reductions in risk for moves southward from either the north or middle tier, and increases in risk for moves northward from the middle tier. Increases similar in magnitude of middle to north did not attain statistical significance in the few southern-born migrants. For the small groups of black men and white men of Korean service, trends were similar but did not attain significance, whereas for white women, they were of borderline significance. Findings imply an environmental cause for MS, with acquisition years before symptom-onset.

The Possible Role of Hepatitis A Virus in the Pathogenesis of Atherosclerosis

The possible association between hepatitis A virus (HAV) infection and coronary artery disease (CAD) was studied. Blood from 391 patients undergoing coronary angiography was tested for serum IgG antibodies to HAV and C-reactive protein (CRP). Of the 391 patients, 205 (52%) had anti-HAV IgG antibodies. CAD prevalence was 74% in HAV-seropositive and 52% in HAV-seronegative patients (P<.0001); significance persisted after adjustment for either traditional CAD risk factors or for risk factors plus other infectious agents (cytomegalovirus, Chlamydia pneumoniae, Helicobacter pylori, and herpes simplex virus). In addition, CRP levels were significantly higher in HAV-seropositive than in HAV-seronegative patients (P=. 013) in both univariate and multivariate analyses. Logistic regression analysis demonstrated that HAV seropositivity is an independent predictor of risk for CAD and elevated CRP levels. HAV infection is therefore associated with CAD, which raises the possibility that this virus may play a causal role in atherogenesis.