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Biomedical subjects

D Sparrow

Publications and source records attributed to D Sparrow.

At least 73 records · Page 4Linked to original sources
PubMed1995

A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: the Normative Aging Study.

It has been hypothesized that nonspecific airway hyperresponsiveness is a risk factor for accelerated pulmonary-function decline during aging and the development of chronic airflow obstruction. We tested this hypothesis in a prospective, longitudinal study of 912 middle-aged and older men (median age, 60 yr; range, 41 to 86 yr) participating in the Normative Aging Study (NAS). Subjects underwent methacholine challenge testing and spirometry at the time of a regularly scheduled NAS examination, and follow-up spirometry was performed after a median interval of 3.3 yr. Allergy skin testing with a panel of four aeroallergens (mixed grasses, mixed trees, ragweed, and house dust) was also performed at the initial examination. Methacholine responsiveness was expressed as the dose-response slope (DRS) (i.e., the slope of a line connecting the origin with the last point of the methacholine dose-response plot) in units of percent decline FEV1/mumol methacholine. The relationship of the methacholine DRS to the subsequent rate of annual decline in lung function (FEV1, FVC, and FEV1/FVC) was examined using multiple linear-regression models with the rates of pulmonary-function decline as the outcome variables. After adjusting for age, height, smoking status, and initial level of lung function, the log10 DRS was a significant predictor of the rate of decline of FEV1 (regression coefficient beta = 12.8, p = 0.03) and FEV1/FVC x 100 (beta = 0.506, p = 0.0001), and a borderline significant predictor of FVC (beta = 15.3, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Chronic respiratory symptoms and airway responsiveness to methacholine are associated with eosinophilia in older men: the Normative Aging Study.

Identification of subsets of patients with chronic obstructive lung disease (COLD) in order to determine disease outcomes and, possibly, the effects of treatment is an area of clinical interest. At present, it remains unclear which patients with COLD are most likely to benefit from anti-inflammatory therapy. We investigated this question in a community-dwelling sample of men. In this study, the relationship of chronic respiratory symptoms, airway responsiveness to methacholine, and skin test reactivity to peripheral-blood eosinophil and neutrophil counts was examined among 894 male participants in the Normative Aging Study (mean age 60 yrs; range 41-90 yrs). The symptoms considered were asthma, persistent wheeze, dyspnoea, chronic cough and phlegm. Responsiveness to methacholine was defined as a provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of < or = 8.6 mumol, a positive skin test as a wheal diameter of > or = 5 mm after subtraction of the diameter of any wheal reaction to a glycerin control, and eosinophilia as an eosinophil count of > or = 275 cells.mm-3 in peripheral blood. Chronic symptoms (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.4-2.7), airway responsiveness (OR 1.7; CI 1.1-2.7), and the combination of symptoms and airway responsiveness (OR 3.4; CI 2.0-5.6) were positively and significantly related to peripheral-blood eosinophil counts. These relationships remained significant after adjustment for the effects of age and smoking, and after exclusion of asthmatic subjects. Symptoms and airway responsiveness combined were not significantly related to neutrophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Low-level lead exposure and renal function in the Normative Aging Study.

Occupational and environmental lead exposure has been associated with significant impairment in renal function. The authors studied the cross-sectional relation between creatinine clearance and blood lead concentration in a population of 744 men participating in the Normative Aging Study of the Department of Veterans Affairs between July 1988 and April 1991. These men, aged 43-90 years, were recruited from communities in the Greater Boston, Massachusetts, area and were selected without regard to lead exposure. The mean values for blood lead concentration and creatinine clearance rate were 8.1 micrograms/dl (standard deviation, 3.9 micrograms/dl) and 88.2 ml/minute (standard deviation, 22.0 ml/minute), respectively. Independent relations of creatinine clearance to blood lead were assessed by multivariate linear regression analysis, with adjustment for various potential confounders. In multivariate linear regression models, the rate of creatinine clearance was significantly and negatively associated with increasing levels of blood lead, even after adjustment for age, body mass index, and use of diuretic and analgesic medications (the beta-coefficient for ln blood lead measured in microgram[microgram/dl]-1 was -0.030; standard error = 0.014, p = 0.037). A rise in ln blood lead of 10.0 micrograms/dl was associated with a decrease in the ln creatinine clearance rate of 10.4 ml/minute. These results support the hypothesis that exposure to low-level environmental lead correlates with a significant decrement in renal function.

Adult↗
PubMed1994

The RSRF/MEF2 protein SL1 regulates cardiac muscle-specific transcription of a myosin light-chain gene in Xenopus embryos.

We have examined the role of two RSRF/MEF2 proteins in the onset of skeletal and cardiac muscle differentiation in early Xenopus embryos. In normal development, zygotic expression of SL1 (MEF2D) precedes that of SL2 (MEF2A) by several hours, but neither gene is expressed prior to the accumulation of MyoD and Myf5 transcripts in the somitic mesoderm. Ectopic expression of the myogenic factors in explants of presumptive ectoderm induces expression of both SL1 and SL2, whereas in reciprocal experiments, neither RSRF protein activates the endogenous myoD or Myf5 genes. We conclude that SL1 and SL2 lie downstream of these myogenic factors in the skeletal myogenic pathway. SL1 is distinguished from SL2 in being expressed in the presumptive heart region of the early tailbud embryo, prior to detection of any markers for cardiac muscle differentiation. Furthermore, ectopic SL1 induces the expression of an endogenous cardiac muscle-specific myosin light-chain (XMLC2) gene in cultured blastula animal pole explants, whereas SL2 has no comparable effect. These results demonstrate that in addition to a possible role in skeletal myogenesis, SL1 also acts in vivo as a regulator of cardiac muscle-specific transcription.

Amino Acid Sequence↗
PubMed1994

The relationship of epinephrine excretion to serum lipid levels: the Normative Aging Study.

Catecholamines are known to stimulate lipolysis of triglyceride stores in adipose tissue. However, the relationship of sympathoadrenal activity to serum lipid and lipoprotein concentrations remains uncertain. Since obesity, particularly the centripetal form, has recently been shown to be associated with increased urinary excretion of norepinephrine and decreased excretion of epinephrine, the possibility that the sympathoadrenal system is involved in the lipid abnormalities associated with the centripetal form of obesity was investigated. The relationship between 24-hour urinary catecholamine excretion and serum lipid and lipoprotein levels was examined among 615 male participants of the Normative Aging Study. Epinephrine excretion was positively correlated with the high-density lipoprotein cholesterol (HDL-C) level and the ratio of HDL-C to low-density lipoprotein cholesterol ([LDL-C] r = .15, P = .0002, and r = .11, P = .007, respectively) and inversely correlated with the triglyceride level (r = -.14, P = .0005). These relationships remained significant after adjusting for the effects of age, smoking, alcohol intake, adiposity, and insulin level. Epinephrine excretion was not significantly related to levels of total cholesterol or LDL-C. Norepinephrine and dopamine excretion were not significantly related to any lipid variable. These data suggest that (1) epinephrine plays an important role in regulating lipid and lipoprotein metabolism in humans, and (2) decreased adrenal medullary activity may contribute to the dyslipidemia (increased triglycerides and decreased HDL-C) commonly observed among the obese. The sympathoadrenal system therefore, along with hyperinsulinemia, may contribute to the increased cardiovascular risk associated with the insulin resistance syndrome.

Adult↗
PubMed1994

Symptoms of anxiety and risk of coronary heart disease. The Normative Aging Study.

BACKGROUND: Several studies have suggested an increased risk of fatal coronary heart disease (CHD) among patients with panic disorder, phobic anxiety, and other anxiety disorders. We prospectively examined this association in the Normative Aging Study. METHODS AND RESULTS: An anxiety symptoms scale was constructed out of five items from the Cornell Medical Index, which was administered to the cohort at baseline. During 32 years of follow-up, we observed 402 cases of incident coronary heart disease (137 cases of nonfatal myocardial infarction, 134 cases of angina pectoris, and 131 cases of fatal CHD: made up of 26 cases of sudden cardiac death and 105 cases of nonsudden death). A nested case-control design (involving 1869 control subjects who remained free of diagnosed CHD) was used to assess the association between anxiety and risk of CHD. Compared with men reporting no symptoms of anxiety, men reporting two or more anxiety symptoms had elevated risks of fatal CHD (age-adjusted odds ratio [OR] = 3.20, 95% confidence interval [CI]: 1.27 to 8.09), and sudden death (age-adjusted OR = 5.73, 95% CI: 1.26 to 26.1). The multivariate OR after adjusting for a range of potential confounding variables was 1.94 (95% CI: 0.70-5.41) for fatal CHD and 4.46 (95% CI: 0.92-21.6) for sudden death. No excess risks were found for nonfatal myocardial infarction or angina. CONCLUSIONS: These data suggest an association between anxiety and fatal coronary heart disease, in particular, sudden cardiac death.

Adult↗
PubMed1994

Predictors of longitudinal change in methacholine airway responsiveness among middle-aged and older men: the Normative Aging Study.

Increasing nonspecific airway responsiveness during aging may precede and predispose to the development of asthma in later life. Characteristics potentially related to longitudinal change in methacholine airway responsiveness were examined over a 3-yr follow-up interval among 435 middle-aged and older men. Initial and follow-up evaluation included spirometry, allergy skin testing with common aeroallergens, measurement of the serum concentration of total IgE, and blood cell counts (total leukocytes and eosinophils, basophils, and neutrophils as a percentage of total leukocytes). The initial values and annual rates of change of these characteristics were examined by multiple linear regression as potential predictors of annual change in methacholine dose-response slope. Annual change in basophil count was directly related to change in dose-response slope (p = 0.02). Initial values and annual rates of change of other cell counts, pulmonary function, allergy skin test reactivity, and serum total IgE concentration were not significantly related to change in dose-response slope. Cigarette smoking history was also not significantly related to longitudinal change in dose-response slope. These data suggest that inflammatory mechanisms involving the basophil may be important in the development of increasing nonspecific airway responsiveness during aging.

Aged↗
PubMed1994

Normal range of methacholine responsiveness in relation to prechallenge pulmonary function. The Normative Aging Study.

Methacholine airway responsiveness has been observed to be related to prechallenge level of pulmonary function; however, normal ranges of responsiveness for specific levels of lung function have not been reported. We examined methacholine airway responsiveness in relation to level of prechallenge pulmonary function in a sample of 547 middle-aged and elderly men who denied any history of respiratory illness or symptoms and who had normal levels of prechallenge FEV1 and FEV1/FVC ratio. The cumulative dose of methacholine provoking a 20 percent decline in FEV1 (PD20FEV1) was positively correlated with prechallenge FEV1 percent predicted (Spearman correlation r = 0.35, p < 0.0001). The fifth percentile of PD20FEV1, chosen as an estimate of the lower limit of the normal range, varied with the level of prechallenge FEV1. When applied to a larger sample of 838 men with normal pulmonary function, the use of FEV1-specific cut-off values to separate "normal" from "abnormal" PD20FEV1 did not improve the sensitivity or specificity of methacholine challenge as a test for questionnaire-reported asthma or wheezing. These data provide lower limits of normal PD20FEV1 which are specific for a subject's prechallenge FEV1; however, these FEV1-specific lower limits of normal PD20FEV1 provided no greater sensitivity and specificity for detecting asthma and wheezing than did a single lower limit of normal PD20FEV1 for all subjects.

Adult↗
PubMed1994

The relationships of abdominal obesity, hyperinsulinemia and saturated fat intake to serum lipid levels: the Normative Aging Study.

Abdominal obesity and hyperinsulinemia are associated with abnormalities in lipid metabolism and are important risk factors for coronary artery disease. Because hyperinsulinemia frequently accompanies abdominal obesity, it is unclear whether each is independently related to lipid abnormalities. Dietary saturated fat may influence these associations since it is associated with elevated lipid levels, obesity and hyperinsulinemia. Abdominal obesity (indexed as abdomen-to-hip circumference ratio), serum insulin level and dietary saturated fat intake were examined in relation to serum levels of lipids and lipoproteins in 878 male participants of the Normative Aging Study. Abdomen-to-hip ratio and insulin level were inversely related to high density lipoprotein cholesterol (HDL-C) (r = -0.17 and -0.21, respectively), and positively related to triglycerides (r = 0.25 and 0.36, respectively). Saturated fat intake was positively related to body mass index (r = 0.20), abdomen-to-hip ratio (r = 0.13), and insulin level (r = 0.10). In multiple linear regression models, abdomen-to-hip ratio was positively related to triglycerides and low density lipoprotein cholesterol (LDL-C) after adjusting for the effects of body mass index, alcohol intake, age, cigarette smoking and physical activity level, but was not significantly related to HDL-C. When serum insulin level was included as a covariate, abdomen-to-hip ratio remained significantly related to LDL-C and triglycerides, although its relationship with triglycerides was attenuated. Insulin level remained inversely related to HDL-C and triglycerides in multivariate models which adjusted for the effects of abdomen-to-hip ratio and BMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1993

Relation between blood lead and urinary biogenic amines in community-exposed men.

The cross-sectional relation between levels of urinary biogenic amines (dopamine, epinephrine, norepinephrine, and serotonin) and levels of blood lead was examined in a study of 645 male participants from a longitudinal study of aging. This stable population of men had initially been recruited from communities in and around Boston, Massachusetts, and had not been selected with regard to lead exposure. Blood lead samples and 24-hour and 2-hour urine specimens were collected during regularly scheduled clinic visits. In multivariate linear regression step-forward models, 24-hour epinephrine excretion was significantly and positively associated with blood lead (beta = 0.101 microgram(microgram/dl)-1 blood lead, SE (standard error) (beta) = 0.045, p = 0.026). Twenty-four-hour norepinephrine excretion was positively associated with blood lead (beta = 0.023 microgram(microgram/dl)-1 blood lead, SE(beta) = 0.029, p = 0.425), and both 24-hour dopamine (beta = -4.35 microgram(microgram/dl)-1 blood lead, SE(beta) = 6.90, p = 0.529) and 2-hour serotonin (beta = -0.348 microgram(microgram/dl)-1 blood lead, SE(beta) = 0.277, p = 0.210) excretion were negatively associated with blood lead; however, these relations did not achieve statistical significance. An increase of 10 micrograms/dl in blood lead was associated with an increase in epinephrine excretion of 11 micrograms/24 hours. These results support the hypothesis that epinephrine metabolism is influenced by low levels of lead exposure.

Adult↗
PubMed1993

New onset wheezing in an older male population: evidence of allergen sensitization in a longitudinal study. Results of the normative aging study.

BACKGROUND: Thirty-nine male subjects, with new-onset wheezing, were selected from participants in the Department of Veterans Affairs Normative Aging Study and compared with 74 age-matched controls. Wheezing was defined by responses to a standardized and regularly administered questionnaire. The subjects with wheezing had a reduced FEV1 compared with controls (p = 0.005), but most had values above 80% predicted. Current smoking was more common in subjects with wheezing (36.8% vs 8.11% in controls, p < 0.001). The mean age of both subjects and controls was 64 years. METHODS: Allergen-specific IgE antibodies were measured, starting with sera at the time of the most recent questionnaire, and on the average 3.1, 7.6, and 12.3 years before that, with use of stored serum samples. RESULTS: Total IgE did not differ significantly between the groups. IgE binding to dust mite antigen was detected in 13% to 15% of the subjects with wheezing compared with fewer than 7% of the controls over four time intervals (p = 0.014). IgE binding to cat and ragweed antigens did not differ significantly between groups. If current nonsmokers were analyzed separately, IgE binding to cat allergen was also slightly greater in subjects with wheezing compared with controls (p = 0.054). Sequential analysis of IgE antibody levels to mite antigen, over time, indicated that IgE antibody antedated the onset of wheezing. CONCLUSIONS: New-onset wheezing in an older adult male population is significantly associated with allergic sensitization to dust mite. There was a borderline association with sensitization to cat in noncurrent smokers only. This supports the hypothesis that a subgroup may have allergic triggers to their symptoms.

Adult↗
PubMed1993

Predictors of the new onset of wheezing among middle-aged and older men. The Normative Aging Study.

Characteristics potentially associated with the development of wheeze symptoms were examined in a prospective cohort study of 624 middle-aged and older men who initially denied any history of wheezing or asthma. Initial evaluation included spirometry, methacholine challenge testing, allergy skin testing with common aeroallergens, serum total IgE concentration, blood leukocyte count, blood eosinophil count, and postural heart rate change (standing minus supine). The presence or absence of wheezing symptoms at follow-up 3 yr later was assessed by questionnaire. Multiple logistic regression was used to examine initial characteristics as predictors of subsequent wheezing. Current smoking was the strongest independent predictor of the new onset of wheezing (adjusted OR, 14.3; 95% confidence interval (CI), 3.9 to 52.3). The risk of developing new wheezing also increased with age (adjusted OR, 1.6; 95% CI, 0.9 to 2.9 comparing individual subjects 10 yr apart) and postural heart rate change at the initial examination (adjusted OR, 1.8; 95% CI, 1.1 to 3.0 comparing individual subjects differing by 10 beats/min). A significant association between greater methacholine airway responsiveness (PD20FEV1 < or = 16.8 mumol versus PD20FEV1 > 16.8 mumol) and the subsequent development of wheezing was observed among nonsmokers (adjusted OR, 5.2; 95% CI, 2.0 to 13.6) but not among current smokers. Other baseline variables were not independently related to the risk of developing wheezing symptoms. These data suggest that current smoking, age, nonspecific airway responsiveness, and altered autonomic function are independently related to the risk of developing wheezing symptoms in middle-aged and older men.

Adult↗
PubMed1993

A longitudinal study of plasma cortisol concentration and pulmonary function decline in men. The Normative Aging Study.

Because of the important role of peripheral airways inflammation in the pathogenesis of asthma and COPD and because of the known anti-inflammatory actions of corticosteroids, we hypothesized that endogenous cortisol may influence the rate of decline of pulmonary function with aging. We examined the basal plasma cortisol concentration and serial spirometric measurements of 86 healthy men participating in the Normative Aging Study. Subjects selected for this study were free of any chronic illnesses and denied chronic use of any medications. Blood for cortisol determination was obtained with the subject in the supine position at 8:00 A.M. Two consecutive spirometric examinations that took place an average of 4.7 yr apart were employed in the analysis. Cross-sectional analysis revealed a weak (p = 0.08) direct relationship between the basal plasma cortisol concentration and FEV1. The cortisol concentration and FVC appeared unrelated. Longitudinal analysis revealed a significant (p = 0.008) relationship between the plasma cortisol concentration and the rate of decline of FEV1 over the follow-up interval after adjustment for age, height, smoking status, and initial FEV1 in a multivariate regression model. This multivariate model predicts that subjects with cortisol concentration 1 standard deviation (23.3 ng/ml) below the mean would experience FEV1 decline 71.6 ml/yr greater than subjects with cortisol concentration 1 standard deviation above the mean. This difference was comparable to the estimated 69.5 ml/yr difference between current and never smokers. Cortisol concentration was unrelated to the rate of decline of FVC. The data suggest that physiologic concentrations of cortisol may modulate the process responsible for the deterioration of ventilatory function with aging.

Aging↗
PubMed1993

Risk factors for ventilatory impairment among middle-aged and elderly men. The Normative Aging Study.

To evaluate the relationship of atopy and inflammation to the occurrence of ventilatory impairment, we studied 1,301 middle-aged and older men participating in the Normative Aging Study at the time of their 1984 to 1987 examination. Screening at entry to the study in the 1960s had excluded subjects with asthma and other chronic diseases at that time. After adjustment for smoking status and pack-years in this cross-sectional analysis, a weak inverse relationship between FEV1 and blood eosinophil count was not statistically significant, and FEV1 showed no relationship to blood eosinophil count as a percentage of total leukocytes. A weak inverse relationship between FEV1 and serum total IgE concentration was not statistically significant. Cutaneous immediate hypersensitivity to one or more common aeroallergens was not related to FEV1. A significant inverse relationship between FEV1 and blood total leukocyte count was observed in never and former smokers. FEV1 was significantly lower in subjects reporting usual phlegm production. These findings suggest that ventilatory impairment is not related to atopic status among middle-aged and older men without a history of asthma. The inverse relationship between total leukocyte count and FEV1 in this sample supports the hypothesis that nonallergic inflammation plays a role in the pathogenesis of chronic airflow obstruction in this group.

Aged↗
PubMed1992

Association of serum albumin with blood pressure in the normative aging study.

Little is known regarding serum albumin's epidemiologic relation to chronic disease. The relation of serum albumin to blood pressure was assessed in a longitudinal study of men who have been seen at 3- to 5-year intervals since the early 1960s. The authors analyzed data from over 20 years of observation using cross-sectional multiple regression models of blood pressure that allow for the correlation between repeated measures on the same individual (GLMIC models), longitudinal GLMIC models that incorporate terms for the interaction of time with serum albumin at baseline, and models of the slope of individuals' blood pressure over time. Serum albumin levels were found to have a consistently strong relation with both systolic blood pressure and diastolic blood pressure in the cross-sectional GLMIC models only. This relation did not change appreciably when covariates for age, body mass index, alcohol ingestion, smoking, serum calcium, hematocrit, heart rate, and antihypertensive medications were added. A rise in serum albumin of 1 g/dl was associated with 1.79-mmHg and 0.91-mmHg increases in systolic blood pressure and diastolic blood pressure, respectively. This phenomenon may be related to experimental studies linking tryptophan, the only amino acid to bind noncovalently to serum albumin, to a blood pressure-lowering effect mediated by promotion of 5-hydroxytryptamine synthesis in the brain.

Adult↗
PubMed1992

Relationship of catecholamine excretion to body size, obesity, and nutrient intake in middle-aged and elderly men.

Catecholamine release from sympathetic nerves and the adrenal medulla is influenced by diet under controlled research conditions. To test whether diet affects catecholamine excretion in free-living men, the urinary content of dopamine (DA), epinephrine (Epi), or norepinephrine (NE) was measured in 24-h collections provided by 572 participants of the Normative Aging Study of the Veterans Administration. Average daily intakes of energy and macronutrients were assessed by means of a semiquantitative food frequency questionnaire and sodium intake by quantitation of sodium excretion. Catecholamine excretion was also examined in relation to anthropometric variables. Because DA and Epi excretion were inversely related to age, all subsequent analyses included adjustments for age. Although DA and NE were positively related to measures of body size and fatness, Epi was negatively related to body fatness. Excretion rates of all three catecholamines were directly related to total energy intake and inversely related to energy-adjusted CHO consumption.

Adult↗
PubMed1992

Upper airway anesthesia delays arousal from airway occlusion induced during human NREM sleep.

Six healthy subjects (5 males and 1 female, 26-40 yr old) were studied during non-rapid-eye-movement (NREM) sleep to assess the role of upper airway (UA) afferents in the arousal response to induced airway occlusion. Subjects wore an airtight face mask attached to a low-resistance one-way valve. A valve in the inspiratory circuit allowed instantaneous inspiratory airway occlusion and release; the expiratory circuit remained unoccluded at all times. Each subject was studied during two nights. On one night, occlusions were created during stable stage 2 NREM sleep before and after application of 4% lidocaine to the oral and nasal mucosa. On the other night, the protocol was duplicated with saline ("sham anesthesia") rather than lidocaine. The order of nights was randomized. Occlusions were sustained until electroencephalographic arousal. Three to 12 occlusions were performed in each subject for each of the four parts of the protocol (pre- and post-lidocaine, pre- and post-saline). The auditory threshold for arousal (1,500-Hz tone beginning at 30 dB) was also tested before and after UA lidocaine. For the group, arousal time after UA anesthesia was prolonged compared with preanesthesia arousal time (P less than 0.001); arousal time after sham anesthesia did not significantly increase from before sham anesthesia (P = 0.9). The increase in arousal time with UA anesthesia was greater than the increase with sham anesthesia (P less than 0.001). The auditory arousal threshold did not increase after UA anesthesia. Inspiratory mask pressure, arterial O2 saturation of hemoglobin, and end-tidal PCO2 during occlusions were similar before and after UA anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗