PubMed Health⌕ Search

Biomedical subjects

D Sparrow

Publications and source records attributed to D Sparrow.

At least 19 recordsLinked to original sources
PubMed2000

Subdivision of the cardiac Nkx2.5 expression domain into myogenic and nonmyogenic compartments.

Nkx2.5 is expressed in the cardiogenic mesoderm of avian, mouse, and amphibian embryos. To understand how various cardiac fates within this domain are apportioned, we fate mapped the mesodermal XNkx2.5 domain of neural tube stage Xenopus embryos. The lateral portions of the XNkx2.5 expression domain in the neural tube stage embryo (stage 22) form the dorsal mesocardium and roof of the pericardial cavity while the intervening ventral region closes to form the myocardial tube. XNkx2.5 expression is maintained throughout the period of heart tube morphogenesis and differentiation of myocardial, mesocardial, and pericardial tissues. A series of microsurgical experiments showed that myocardial differentiation in the lateral portion of the field is suppressed during normal development by signals from the prospective myocardium and by tissues located more dorsally in the embryo, in particular the neural tube. These signals combine to block myogenesis downstream of XNkx2.5 and at or above the level of contractile protein gene expression. We propose that the entire XNkx2.5/heart field is transiently specified as cardiomyogenic. Suppression of this program redirects lateral cells to adopt dorsal mesocardial and dorsal pericardial fates and subdivides the field into distinct myogenic and nonmyogenic compartments.

Animals↗
PubMed1999

Relations between individual and neighborhood-based measures of socioeconomic position and bone lead concentrations among community-exposed men: the Normative Aging Study.

To examine the association between lead exposure and both individual and geographic area indicators of socioeconomic position, the authors measured tibia lead concentration, a biomarker of cumulative lead exposure, using K x-ray fluorescence in a cross-sectional survey of 538 white males aged 50-92 years who were healthy when enrolled in the Normative Aging Study (Boston, Massachusetts) in the 1960s. Data on individual risk factors, education, occupation, and income were collected by questionnaire. Using subjects' residential addresses at the time of the tibia lead measurements, the authors obtained geographic area-specific measures of education, social class, and poverty by linking records to 1990 US Census block group data. In multivariate linear regression analysis controlling for age and cumulative smoking, tibia lead concentrations were 10.39 microg/g (95% confidence interval (CI) 7.80-12.97) higher in men who did not graduate from high school than in men with > or =4 years of college. Among the former men (non-high school graduates), living in an undereducated area was associated with a 9.28 microg/g (95% CI 1.59-16.97) increase in tibia lead level compared with living in a non-undereducated area; among the latter men (college graduates), no difference existed by residential area education (beta = 0.72, 95% CI -5.35 to 6.78). The authors conclude that the influence of individual socioeconomic position on cumulative lead exposure is modified by geographic area conditions.

Adult↗
PubMed1999

Relationship of lead in drinking water to bone lead levels twenty years later in Boston men: the Normative Aging Study.

Tap water in a city like Boston, which has old houses containing lead plumbing, is known to be a significant source of potential lead exposure. Bone lead levels integrate exposure over many years, and in vivo bone lead measurements have recently become possible with the advent of K x-ray fluorescence instruments. Thus we examined the relationship between first morning tap-water lead levels measured in homes in the 1970s and levels of lead in bone measured in the 1990s among middle-aged to elderly men who lived in those homes. We studied 129 participants in the Normative Aging Study who had lead measured in their homes' tap water in 1976 and 1977 by graphite furnace-atomic absorption spectrophotometry. From 1991 to 1995, the same subjects had blood lead levels measured by graphite furnace-atomic absorption spectroscopy and tibia and patella bone lead levels measured by K x-ray fluorescence. We ran multivariate linear regression models predicting bone lead levels that adjusted for factors which had previously been linked with this outcome in the Normative Aging Study (age, pack-years of smoking, and educational level). Among subjects who lived in houses with > or = 50 micrograms lead/liter of first morning tap water representing water that had been standing overnight in the plumbing in 1976 and 1977, those who reported medium or high levels of tap-water ingestion (> or = 1 glass/day) had progressively higher patella lead levels than did those with low levels of ingestion (< 1 glass/day). No such relationship was found among subjects who lived in houses with < 50 micrograms lead/liter of first morning tap water in 1976 and 1977. We conclude that ingestion of lead-contaminated tap water is an important predictor of elevated bone lead levels later in life.

Adult↗
PubMed1999

The FEF25-75/FVC ratio is associated with methacholine airway responsiveness. The normative aging study.

Airway responsiveness is known to be partly explained by geometric and anatomic factors. This cross-sectional investigation was undertaken to determine whether FEF25-75/FVC as a surrogate measure of airway size relative to lung size is associated with airway responsiveness to methacholine. Posteroanterior chest radiographs and spirometry were performed on a group of 929 middle aged and older men from an ongoing longitudinal study, the Normative Aging Study, who returned for their regularly scheduled examination between 1984 and 1989. Subjects had a mean age of 60.5 +/- 7.7 yr. FEV1, FEF25-75, and FVC were taken from spirometric results and FEF25-75/FVC ratios were obtained. Main bronchus (MB) and tracheal (TR) diameters and lung area (LA) were obtained from chest radiographs, and ratios of MB/LA and TR/LA were calculated for each subject and compared with FEF25-75/ FVC as measures of airway size relative to lung size. In a multiple linear regression model adjusting for age, height, initial FEV1, smoking, eosinophil count, and IgE level, FEF25-75/FVC was significantly related to the degree of methacholine airway responsiveness as measured by Log10 dose response slope (beta = -0.37, p < 0.001). Controlling for the same variables, both MB/LA (beta = -149.07, p < 0.001) and TR/LA (beta = -125.87, p < 0.001) were significant predictors of the degree of bronchial responsiveness in separate regression models; however, their effects were greatly attenuated when FEF25-75/ FVC was present in the same model. Similar results were obtained after excluding subjects with FEV1/ FVC </= 0.70 and subjects who had any smoking history. We conclude that FEF25-75/FVC as a surrogate measure of airway size relative to lung size is significantly associated with airway responsiveness.

Adult↗
PubMed1999

The independent contribution of bone and erythrocyte lead to urinary lead among middle-aged and elderly men: the normative aging study.

Plasma is the component of blood from which lead is free to cross cell membranes and cause organ toxicity. Plasma lead levels, however, are extremely low and difficult to measure. Urinary lead originates from plasma lead that has been filtered at the glomerular level; thus, urinary lead adjusted for glomerular filtration rate serves as a proxy for plasma lead levels. In this investigation we examined the interrelationships of lead levels in whole blood corrected by hematocrit [i.e., erythrocyte lead (EPb)], trabecular bone (TBoPb), cortical bone (CBoPb), and urine excreted over 24 hr (UPb); all samples were obtained from 71 middle-aged and elderly men with no known occupational lead exposures. Lead was measured by graphite furnace atomic absorption spectroscopy (blood), K-X-ray fluorescence (bone), and inductively coupled plasma mass spectroscopy (urine). Lead levels were generally low, with mean EPb, TBoPb, and CBoPb values of 13.8, 31.1, and 21.7 microg/g, respectively, and a median UPb value of 6.15 microg/day. In generalized additive models adjusted for body weight and creatinine clearance rate, both EPb and bone lead variables remained independently and significantly associated with UPb. This finding suggests that bone influences plasma lead in a manner that is independent of the influence of erythrocytic lead on plasma lead. Thus, the superiority of bone lead over blood lead in predicting some chronic forms of toxicity may be mediated through bone's influence on plasma lead. In addition, this study suggests that measurement of urinary lead might be useful as a proxy for plasma lead levels in studies of lead toxicity.

Aged↗
PubMed1998

Depression and the risk of coronary heart disease in the Normative Aging Study.

Increasing evidence supports an association between symptomatic depression and the risk of coronary heart disease (CHD), although no single study has compared multiple depression scales. We hypothesized that higher levels of symptomatic depression assessed from different depression scales were associated with the risk of CHD. We examined this relation in the Normative Aging Study, a prospective cohort of older men. A total of 1,305 men free of diagnosed CHD in 1986 completed the revised Minnesota Multiphasic Personality Inventory (MMPI-2). We categorized scores for the MMPI-2 D, MMPI-2 DEP, and Symptom Checklist-90 (SCL-90) depression scales. During an average 7.0 years of follow-up, 110 cases of incident CHD occurred, including 30 cases of nonfatal myocardial infarction, 20 cases of fatal CHD, and 60 cases of angina pectoris. Compared with men reporting the lowest level of depression, men in the highest level of depression had multivariate-adjusted relative risks of incident CHD (total CHD and angina) of 1.46 (95% confidence interval 0.83 to 2.57), 2.07 (95% confidence interval 1.13 to 3.81), and 1.73 (95% confidence interval 0.97 to 3.10) for the MMPI-2 D, MMPI-2 DEP, and SCL-90 scales, respectively. Similar RRs were obtained for each CHD subtype according to each depression scale. We found strong dose-response relations between level of depression measured by the MMPI-2 DEP scale and incidence of both angina pectoris (p value for trend, 0.039) and CHD (p value for trend, 0.016). Among older men, symptomatic depression measured by any of 3 depression scales may be positively associated with the risk of CHD.

Aging↗
PubMed1998

Prospective study of a self-report type A scale and risk of coronary heart disease: test of the MMPI-2 type A scale.

BACKGROUND: Several methods exist by which to assess type A behavior (TAB). Although the videotaped clinical interview is regarded as the "gold standard," self-report measures have also proved useful in assessing TAB in large population studies. The purpose of this study was to examine prospectively the relationship of TAB to risk of coronary heart disease (CHD) incidence with the use of the revised Minnesota Multiphasic Personality Inventory (MMPI-2) Type A Scale. To the best of our knowledge, this is the first test of this scale in the context of predicting CHD incidence. METHODS AND RESULTS: The study was performed in the VA Normative Aging Study, an ongoing cohort of older (mean age, 61 years) community-dwelling men. A total of 1305 men who were free of diagnosed CHD in 1986 completed the MMPI-2 Type A Scale. During an average 7.0 years of follow-up, 110 cases of incident CHD occurred. Compared with men in the lowest quartile of type A scores, men in the highest quartile had multivariate adjusted relative risks of 2.86 (95% CI, 1.19 to 6.89; P for trend=0.016) for combined CHD death and nonfatal myocardial infarction (MI) and 2.30 (95% CI, 1.32 to 4.01; P for trend=0.001) for combined CHD death/nonfatal MI plus angina pectoris. The relationship of TAB to CHD was independent of measures of anger and cynicism. CONCLUSIONS: The MMPI-2 Type A Scale predicts CHD incidence. Further research is warranted to examine the correlation, if any, between this scale and the videotaped clinical interview.

Adult↗
PubMed1998

Relation of nutrition to bone lead and blood lead levels in middle-aged to elderly men. The Normative Aging Study.

The relations of nutritional factors to lead accumulation in the body were examined cross-sectionally among 747 men aged 49-93 years (mean 67 years) in the Normative Aging Study in 1991-1995. Means (standard deviations) for blood lead, tibia lead, and patella lead were 6.2 (4.1) microg/dl, 21.9 (13.3) microg/g, and 32.0 (19.5) microg/g, respectively. In multiple regression models adjusting for age, education level, smoking, and alcohol consumption, men in the lowest quintile of total dietary intake levels of vitamin D (including vitamin supplements) (<179 i.u./day) had mean tibia and patella lead levels 5.6 microg/g and 6.0 microg/g higher than men with intake in the highest quintile (> or =589 i.u./day). Higher calcium intake was associated with lower bone lead levels, but this relation became insignificant when adjustment was made for vitamin D. The authors also observed inverse associations of blood lead levels with total dietary intake of vitamin C and iron. When analyses were controlled for patella lead, age, smoking, and alcohol consumption, men in the lowest vitamin C intake quintile (<109 mg/day) had a mean blood lead level 1.7 microg/dl higher than men in the highest quintile (> or =339 mg/day), while men in the lowest iron intake quintile (<10.9 mg/day) had a mean blood lead level 1.1 microg/dl higher than men in the highest quintile (> or =23.5 mg/day). This study suggests that low dietary intake of vitamin D may increase lead accumulation in bones, while lower dietary intake of vitamin C and iron may increase lead levels in the blood.

Aged↗
PubMed1998

Temporal relations between obesity and insulin: longitudinal data from the Normative Aging Study.

Although obesity and insulin levels are generally associated in cross-sectional data, the temporal and causal nature of their association is not yet clear. Increased obesity may have preceded increased insulin levels or vice versa. The authors examined the temporal relations between fasting insulin blood levels and weight in longitudinal data from the ongoing Normative Aging Study. Two insulin measurements from which a rate of change (delta Insulin) could be calculated were available from 376 non-diabetic male subjects (mean age = 62.1 years). Rate of change in weight could be calculated for the previous inter-examination period (delta Weight1), the contemporaneous period (delta Weight2), and the inter-examination period following the second insulin measurement (delta Weight3). delta Weight2 was a significant predictor (p = 0.0005) of delta insulin in multiple linear regression models that included control for potential confounders (body mass index, waist-to-hip ratio, antihypertensive and diuretic medication use, and age) and for correlation between the initial level and change in insulin (mean fasting insulin). delta Weight1 was added to the model and was found not to be statistically significant (p = 0.15). When the model was stratified by age tertile, the regression coefficient on delta Weight1 was -0.44 (p = 0.018) for the youngest stratum, -0.06 (p = 0.72) for the middle stratum, and 0.21 (p = 0.19) for the oldest men. Similarly, delta Insulin was a significant predictor of delta Weight3 (p = 0.026) in a separate regression model. These findings are consistent with both possible temporal sequences of association between changes in insulin and obesity. The intricate homeostatic mechanisms that regulate changes in insulin and obesity may not be readily amenable to description in terms of cause and effect.

Aged↗
PubMed1998

Anxiety and coronary heart disease: a synthesis of epidemiological, psychological, and experimental evidence.

The purpose of this review is to examine the epidemiological, psychological, and experimental evidence for an association between anxiety and coronary heart disease (CHD). Papers published during the years 1980-1996 on anxiety and CHD and relevant publications from earlier years were selected for this review. Epidemiologic evidence suggests that anxiety may be a risk factor for the development of CHD. Chronic anxiety may increase the risk of CHD by: (a) influencing health behaviors (e.g. smoking); (b) promoting atherogenesis (e.g. via increased risk of hypertension); and (c) triggering fatal coronary events, either through arrhythmia, plaque rupture, coronary vasospasm, or thrombosis. Electrophysiologic evidence is particularly compelling: anxiety appears to be associated with abnormal cardiac autonomic control, which may indicate increased risk of fatal ventricular arrhythmias. The strength, consistency, and dose-response gradient of the association between anxiety and CHD, together with the biologic plausibility of the experimental evidence, suggest that anxiety may contribute to risk of CHD and that the relationship warrants further investigation.

Anxiety Disorders↗
PubMed1998

Indoor allergens and longitudinal FEV1 decline in older adults: the Normative Aging Study.

We investigated the relationship between home allergen exposure and decline in FEV1 in 10 asthmatic and 30 randomly selected, age-matched, nonasthmatic participants in the Normative Aging Study. We defined asthma as subject-reported wheezing apart from colds, with either a physician's diagnosis of asthma or a methacholine PD20 FEV1 of 8.6 micromol or less. We examined the relationship between the annual decline in FEV1 and the concentrations of the cockroach (Blattella germanica) allergens Bla g 1 and Bla g 2, the dust mite (Dermatophagoides pteronyssinus and Dermatophagoides farinae) allergens Der p 1 and Der f 1, and the cat (Felis domesticus) allergen Fel d 1 in house dust specimens. Bla g 1 (-79.8 ml/yr, p = 0.0006) and Bla g 2 (-40.81 ml/yr, p = 0.0004) were significant predictors of decline in FEV1 after adjustment for age, smoking, and baseline FEV1. These results were unchanged after elimination of the asthmatic subjects from the analysis. We conclude that cockroach allergen levels in homes is a risk factor for accelerated decline in FEV1 independent of airway responsiveness.

Adult↗
PubMed1998

Impaired ventilatory function and elevated insulin levels in nondiabetic males: the Normative Aging Study.

Lower levels of baseline ventilatory function have consistently been associated with increased risk of cardiovascular mortality in prospective studies, but the underlying mechanisms are not known. Increased risk of coronary heart disease is associated with higher serum insulin levels. This report examines the relationship between ventilatory function and indirect measures of insulin resistance. Cross-sectional data from 922 nondiabetic participants in the Normative Aging Study were analysed using multiple linear regression models with adjustment for potential confounders. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined in relation to indicators of insulin resistance, i.e. fasting insulin and the fasting insulin resistance index (FIRI). Diabetics were excluded because impaired insulin secretion interferes with the validity of these as measures of insulin resistance. Fasting insulin and FIRI were negatively correlated with FVC and FEV1 (all p< 0.001). These associations persisted after adjusting for potential confounders including age, height, body mass index, waist to hip circumference ratio, physical activity, alcohol intake and smoking in separate multiple linear regression models, for both insulin (all p< or =0.0008) and FIRI (all p< or =0.0001). Negative cross-sectional associations between ventilatory function and indirect measures of insulin resistance were found in nondiabetic males. Insulin resistance may contribute to the previously unexplained association between ventilatory function impairment and cardiovascular mortality. Mechanisms underlying the relationship between insulin resistance and decreased ventilatory function remain to be elucidated.

Adult↗
PubMed1998

Baseline ventilatory function predicts the development of higher levels of fasting insulin and fasting insulin resistance index: the Normative Aging Study.

A consistent but as yet unexplained association between baseline ventilatory function and risk of coronary heart disease (CHD) has been reported from many prospective studies. Insulin-resistant states are associated with increased risk of CHD. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow rate (MMEF) at study entry were examined as predictors for indirect measures of insulin resistance after a mean follow-up interval of 20.9 yrs in 1050 nondiabetic male subjects in the Normative Aging Study. Males in the top quintile of insulin or fasting insulin resistance index (FIRI) levels at follow-up were defined as being relatively insulin resistant. FVC was negatively associated with risk of being relatively insulin resistant using the insulin (p=0.002) or FIRI (p=0.0001) criteria at follow-up in logistic regression models adjusting for baseline age, body mass index, fat distribution pattern and cigarette smoking. Similar associations were found for FEV1 and MMEF. Additional adjustment for baseline postcarbohydrate challenge glucose levels made little difference to the results, suggesting that baseline glucose intolerance was not a significant source of bias. These findings are consistent with the possibility that insulin resistance may be one of the factors mediating the previously unexplained prospective association between impairment of ventilatory function and risk of mortality from coronary heart disease.

Adult↗
PubMed1998

The association between alveolar bone loss and pulmonary function: the VA Dental Longitudinal Study.

The effect of oral conditions on medical outcomes is not well understood. The purpose of this epidemiological investigation was to examine whether the risk for chronic obstructive pulmonary disease (COPD) is enhanced among individuals with a history of periodontal disease as assessed by radiographic alveolar bone loss (ABL). Subjects were selected from the VA Dental Longitudinal Study, a long-term study of aging and health in male veterans who were medically healthy at baseline. Subjects are not VA patients. Those subjects with a forced expiratory volume in 1 second (FEV1) less than 65% of predicted volume were categorized as having COPD. ABL was assessed by using full-mouth series periapical films measured by a Schei ruler. Bone loss at each interproximal site was measured in 20% increments, and the mean whole-mouth bone loss score was calculated. Logistic regression analysis was used to determine the independent contribution of bone loss measurement at baseline to the subsequent risk of developing COPD over a 25-year follow-up period. Covariates included measures of smoking, height, age, education, and alcohol consumption. Of the 1,118 medically healthy dentate men at baseline, 261 subsequently developed COPD. We found that ABL status at baseline was an independent risk factor for COPD, with subjects in the worst population quintile of bone loss (mean ABL > 20% per site) found to be at significantly higher risk (OR = 1.8; 95% CI = 1.3, 2.5). The results of this analysis indicate that increased ABL is associated with an increased risk for COPD

Adult↗
PubMed1997

Age and secular trends in bone lead levels in middle-aged and elderly men: three-year longitudinal follow-up in the Normative Aging Study.

The goal of this study was to examine age and secular trends in bone and blood lead levels of community-exposed men. Bone and blood lead levels were measured twice, with a 3-year interval between measurements, among participants in a longitudinal study of aging. Seventy subjects (mean age = 66 years, age range = 52-83 years) with repeated measurements of bone and blood lead levels were studied. At the first evaluation, geometric mean lead levels in patella, tibia, and blood were 29.1 (standard deviation (SD) 1.8) microg/g, 17.5 (SD 2.0) microg/g, and 6.7 (SD 1.8) microg/dl, respectively. At the second evaluation, these levels were 22.2 (SD 1.8) microg/g, 17.9 (SD 1.7) microg/g, and 5.1 (SD 1.4) microg/dl, respectively. Cross-sectional analysis of each set of measurements indicated that, on average, a 1-year-older individual would have 2.7% and 2.4-3.2% higher levels of lead in patella and tibia, respectively. In contrast to the increasing age trend in cross-sectional analysis, the secular trend over time was decreasing for patella lead levels and stable for tibia lead levels. The authors conclude that in community-exposed middle-aged and elderly men, the biomarkers of exposure to lead are decreasing in patella and blood and unchanging in tibia as of the early 1990s. The increasing age trend in bone lead levels in cross-sectional studies should be carefully interpreted in light of the birth cohort effect.

Aged↗
PubMed1997

Alcohol intake and insulin levels. The Normative Aging Study.

Much remains to be clarified in the apparently protective effect of moderate alcohol use against coronary heart disease risk. Insulin levels are positively associated with coronary heart disease risk, so recent reports of decreased insulin sensitivity among nondrinkers and lower fasting insulin levels with increasing alcohol intake suggest the possibility that insulin may play a role. Between 1987 and 1991, the authors examined fasting insulin concentrations and the empiric fasting insulin resistance index in relation to reported alcohol intake (mean, 15.3 g/day; standard deviation, 19.6; range, 0-120.6) and potential confounders. The latter included age, obesity, fat distribution, smoking, energy, saturated fat intake, antihypertensive medication, and physical activity. Participants in this cross-sectional analysis were 938 nondiabetic men from the Boston, Massachusetts, area who were part of the Normative Aging Study. Unadjusted fasting insulin levels were significantly different (p = 0.008) between categories of alcohol intake, as were fasting insulin resistance index values (p = 0.01). After adjustment for potential confounders, analysis revealed that subjects consuming moderate amounts of alcohol had the lowest fasting insulin and fasting insulin resistance index values. Compared with values from moderate drinkers, fasting insulin resistance index values were higher in those subjects reporting no alcohol intake (p = 0.011), low intake (p = 0.004), and high intake (p = 0.04). A similar pattern was observed for fasting insulin values. Among this sample of nondiabetic men, moderate drinkers had the lowest levels of fasting insulin resistance index and fasting insulin, consistent with lower levels of insulin resistance and thus lower risk for coronary heart disease. These findings suggest the possibility that the coronary heart disease-protective effects of moderate alcohol use are at least partially mediated by insulin.

Adult↗
PubMed1997

Is worrying bad for your heart? A prospective study of worry and coronary heart disease in the Normative Aging Study.

BACKGROUND: Worry is an important component of anxiety, which recent work suggests is related to increased incidence of coronary heart disease (CHD). Chronic worry has also been associated with decreased heart rate variability. We hypothesized that high levels of worry may increase CHD risk. METHOD AND RESULTS: We examined prospectively the relationship of worry with CHD incidence in the Normative Aging Study, an ongoing cohort of older men. In 1975, 1759 men free of diagnosed CHD completed a Worries Scale, indicating the extent to which they worried about each of five worry domains: social conditions, health, financial, self-definition, and aging. During 20 years of follow-up, 323 cases of incident CHD occurred: 113 cases of nonfatal myocardial infarction (MI); 86 cases of fatal CHD; and 124 cases of angina pectoris. Worry about social conditions was the domain most strongly associated with incident CHD. Compared with men reporting the lowest levels of social conditions worry, men reporting the highest levels had multivariate adjusted relative risks of 2.41 (95% CI, 1.40 to 4.13) for nonfatal MI and 1.48 (95% CI, 0.99 to 2.20) for total CHD (nonfatal MI and fatal CHD). A dose-response relation was found between level of worry and both nonfatal MI (P for trend, .002) and total CHD (P for trend, .04). CONCLUSIONS: These results suggest that high levels of worry in specific domains may increase the risk of CHD in older men.

Adult↗