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Biomedical subjects

M F Muldoon

Publications and source records attributed to M F Muldoon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Assessing the observed relationship between low cholesterol and violence-related mortality. Implications for suicide risk.

Health advocacy groups advise all Americans to restrict their dietary intake of saturated fat and cholesterol as an efficacious and safe way to lower plasma cholesterol concentrations and thus reduce the risk of coronary heart disease and other atherosclerotic disorders. However, accumulating evidence suggests that naturally low or clinically reduced cholesterol is associated with increased nonillness mortality (principally suicide and accidents). Other evidence suggests that such increases in suicide and traumatic death may be mediated by the adverse changes in behavior and mood that sometimes accompany low or reduced cholesterol. These observations provided the rationale for an ongoing series of studies in monkeys designed to explore the hypothesis that alterations in dietary or plasma cholesterol influence behavior and that such effects are potentiated by lipid-induced changes in brain chemistry. In fact, the investigations in monkeys reveal that reductions in plasma cholesterol increase the tendency to engage in impulsive or violent behavior through a mechanism involving central serotonergic activity. It is speculated that the cholesterol-serotonin-behavior association represents a mechanism evolved to increase hunting or competitive foraging behavior in the face of nutritional threats signaled by a decline in total serum cholesterol (TC). The epidemiological and experimental data could be interpreted as having two implications for public health: (1) low-cholesterol may be a marker for risk of suicide or traumatic death and (2) cholesterol lowering may have adverse effects for some individuals under some circumstances.

Animals↗
PubMed1997

Effects of lovastatin on the immune system.

Laboratory investigations have demonstrated that blockade of HMG-CoA reductase in vitro reduces lymphocyte proliferation in response to mitogens as well as other facets of the immune system, such as natural killer cell cytotoxicity. However, in this randomized and double-blind clinical investigation, treatment with 20-mg lovastatin for 6 months did not significantly alter several enumerative and functional characteristics of circulating immune cells.

Adult↗
PubMed1997

Immune system differences in men with hypo- or hypercholesterolemia.

Substantial epidemiologic evidence indicates that relative hypocholesterolemia in apparently healthy individuals is associated with increased subsequent mortality from cancer and other nonatherosclerotic causes of death. To test a hypothesis potentially underlying these unexplained associations, we evaluated whether individuals with hypo- and hypercholesterolemia differ in various enumerative and functional indices of the immune system. Nineteen healthy adult men with a mean age of 46 years and a mean total cholesterol concentration of 151 mg/dl constituted a low cholesterol group and were compared with 39 men of a similar age whose total cholesterol averaged 261 mg/dl. Relative to the high cholesterol group, hypocholesterolemic men had significantly fewer circulating lymphocytes, fewer total T cells, and fewer CD8+ cells (P's < 0.05). Trends toward fewer CD4+ cells and less IL-2 release in response to PHA were also noted in the low, compared to the high, cholesterol group. The low and high cholesterol groups did not differ in number of B lymphocytes, level of PHA-induced proliferation, number of natural killer (NK) cells, or degree of NK cytotoxicity. These data provide preliminary evidence of immune system differences in healthy individuals with hypo- and hypercholesterolemia.

Adult↗
PubMed1997

Lymphocyte subset redistribution during acute laboratory stress in young adults: mediating effects of hemoconcentration.

Acute psychological stress is known to alter the distribution of circulating lymphocyte subsets and also to cause a reduction of plasma volume. Data were reanalyzed from 4 previously reported studies (E. A. Bachen et al., 1995; T. B. Herbert et al., 1994; A. L. Marsland, S. B. Manuck, T. V. Fazzari, C. J. Stewart, & B. S. Rabin, 1995; A. L. Marsland, S. B. Manuck, P. Wood, et al., 1995) to determine the extent to which changes in the concentration of lymphocyte subsets are attributable to such hemoconcentration. Meta-analytic procedures showed circulating concentrations of T-suppressor/cytotoxic (CD8) and natural killer (NK) cells to increase following acute laboratory challenge, whereas T-helper (CD4) and B- (CD19) cell populations did not change. Adjustments for concomitant hemoconcentration reduced the magnitude of stress-related increases in CD8 and NK cells significantly and revealed a decrease in CD4 and CD19 cell concentrations from baseline to stress measurements. These data provide evidence (a) that increases in circulating numbers of CD8 and NK cells following acute stress are partially attributable to hemoconcentration and (b) that CD4 and CD19 cell concentrations decrease during acute stress when hemoconcentration is taken into account.

Adult↗
PubMed1997

Self-reported levels of anxiety do not predict neuropsychological performance in healthy men.

It is widely believed that even mild to moderately severe levels of anxiety have a negative impact on neuropsychological performance. To test that possibility, we used scores from Spielberger's State and Trait Anxiety scales to predict performance on measures of attention, learning, memory, mental flexibility, and eye-hand coordination. Two samples of healthy young and middle-aged men were studied. Sample 1 consisted of 125 university students (M age = 20.37); Sample 2 consisted of 50 men recruited from the community (M age = 40.64). Results of multiple regression analyses revealed no significant associations in either sample, after controlling for age, education, and average alcohol consumption. These findings suggest an absence of relationship between self-reported symptoms of anxiety and neuropsychological function in healthy men.

Journal Article↗
PubMed1996

D,L-fenfluramine challenge test: experience in nonpatient sample.

The plasma prolactin response to a single-dose fenfluramine challenge is increasingly utilized in psychiatric research as an indirect and noninvasive measure of central serotonergic activity. However, the influences of age, gender, and body weight on prolactin response and characterization of physical and psychological symptoms evoked by fenfluramine remain poorly studied. In the current study, 83 nonpatient male and female volunteers, 25-60 years old, were administered a standardized fenfluramine challenge test (60 mg). Serial blood samples for plasma drug concentration and plasma prolactin concentration were obtained and side effects reported by participants were recorded. Analyses revealed that both plasma drug concentration and prolactin response were correlated with weight-relative dose (r = 0.43 and r = 0.38, respectively; p < 0.001). No significant relationship was noted between prolactin response and either age or gender. Symptoms during fenfluramine challenge were reported by 90% of subjects, most commonly fatigue, headache, lightheadedness, and difficulty concentrating. Overall side effect severity was related to weight-relative dose (r = 0.26; p < 0.05) and prolactin response (r = 0.42; p < 0.001). We conclude that fenfluramine challenge results should be reported as change in plasma prolactin relative to dose, and that in nonpatient samples the test is associated with frequent side effects.

Adult↗
PubMed1996

Absence of enhanced sympathoadrenal activity and behaviorally evoked cardiovascular reactivity among offspring of hypertensives.

To determine whether offspring of hypertensives show enhanced sympathetic nervous system activity, we evaluated several indices of sympathoadrenal activation and cardiovascular responsiveness to behavioral stimuli among 90 normotensive, young adult men having either one or two hypertensive parents (PH+(-), PH++) or normotensive parents only (PH--) (n = 30/group). Measurements included heart rate (HR) and blood pressure (BP) reactions to three mental stressors (the Stroop test, mental arithmetic, mirror tracing), a cold pressor test, postural adjustment (60 degrees upright tilt), isometric exercise and bicycle ergometry, as well as the 24-h excretion of catecholamines (epinephrine [E], norepinephrine [NE]) and venous plasma catecholamine concentrations, both at rest (seated and supine) and in response to the Stroop test and upright tilt. The three groups did not differ in age, education, body mass index (BMI), estimated aerobic fitness, resting HR, cardiac preejection period (PEP) and PEP:LVET (left ventricular ejection time) ratio, 24-h Na or K excretion, or fasting lipids, insulin or plasma renin activity. Resting systolic and diastolic BP varied as a function of parental hypertension, and were significantly higher in PH++ than among PH-- subjects (P < .05). No significant group difference was observed on any measure of plasma or urinary catecholamines, nor did offspring of hypertensives (PH++ or PH+-) showed greater HR or BP reactions than PH-- subjects to any of the several laboratory challenges. In sum, we find no evidence of enhanced sympathetic activity or heightened cardiovascular responsiveness among normotensive young adults who are familially predisposed to essential hypertension.

Adolescent↗
PubMed1996

Hypertension and neuropsychological performance in men: interactive effects of age.

Potentially interactive effects of hypertension and age on the performance of neuropsychological and information processing tests were examined in 123 untreated hypertensive and 50 normotensive men. After covarying education, average alcohol consumption, trait anxiety, and depression scores, results indicated an interaction of age and hypertension. Young hypertensive men (23-40 years) scored significantly worse than young normotensive men on tests of attention/executive function and working memory; middle-aged hypertensive (41-56 years) and normotensive participants were not distinguished by any measures. Hypertensive men performed significantly more poorly than normotensive men on tests of manual dexterity. Results suggest that neuropsychological sequelae of hypertension are more pronounced in young than in middle-aged hypertensive individuals and are independent of various demographic, psychosocial, and alcohol-related factors.

Adult↗
PubMed1996

Serum total antioxidant activity in relative hypo- and hypercholesterolemia.

Individuals with low serum cholesterol experience greater than expected age-adjusted mortality from non-atherosclerotic diseases, including cancer, respiratory and digestive illnesses, but the basis for these associations remains unclear. The current investigation considered the hypothesis that hypocholesterolemia is associated with reduced antioxidant reserve. Serum total antioxidant activity as well as concentrations of vitamin E, vitamin C, and thiols were compared in two groups of 24 subjects distinct in both mean low density lipoprotein (LDL) cholesterol (2.3 v. 4.9 mM) and mean total cholesterol (4.3 v. 7.0 mM). The low and high cholesterol groups were equivalent in gender mix, age, weight, and serum total protein. Results reveal that compared with the high group, the low cholesterol group had decreased total serum antioxidant activity (p < .05). Thiol concentrations were also lower in the low cholesterol group (p < .05). Group differences in serum total antioxidant activity and thiol concentration were larger among men than women. The two groups did not differ in vitamin C. Low cholesterol was associated with reduced absolute vitamin E levels, although the tocopherol: cholesterol ratio was the same in low and high cholesterol individuals. These data indicate that hypocholesterolemia may be associated with low serum antioxidant reserve, possibly increasing susceptibility to oxidative stress.

Adult↗
PubMed1995

Effects of acute psychological stress on serum lipid levels, hemoconcentration, and blood viscosity.

BACKGROUND: While there is substantial evidence that psychological stress enhances risk for coronary artery disease, the mechanisms underlying such an influence remain unclear. We examined the effects of short-term psychological stress on serum lipid levels, hemoconcentration, fibrinogen level, and plasma viscosity. METHODS: Forty-four healthy young adults were randomly assigned to perform a distinctly frustrating cognitive task for 20 minutes (stress condition) or to rest quietly for the same period (control condition). RESULTS: Relative to controls, stressed subjects showed significant increases in blood pressure and heart rate; total, low-density, and high-density lipoprotein cholesterol levels; hematocrit; hemoglobin level; and total protein concentration. Stressed subjects also showed significant reductions in plasma volume and increased plasma viscosity and estimated whole-blood viscosity compared with controls. A similar trend in fibrinogen level was not statistically significant. Individual differences in blood pressure and heart rate response to stress correlated highly with changes in total cholesterol levels and hematocrit. CONCLUSIONS: Our investigation provides further evidence that exposure to short-term mental stress elicits hemoconcentration with associated increases in serum lipid concentrations, hemostatic factors, and blood viscosity.

Acute Disease↗
PubMed1995

Beta 2-adrenergic receptor density and cardiovascular response to mental stress.

In this study we evaluated effects of an acute experimental stressor on beta 2-adrenoceptor density and examined the relationships of baseline receptor density to cardiovascular reactions induced by stress. In addition, we investigated whether any observed alterations in receptor density were associated with concomitant redistribution of circulating lymphocyte populations. Receptor density and lymphocyte subsets were determined before and immediately following performance of a frustrating laboratory task in 22 male volunteers. Blood pressure, heart rate (HR), and plasma catecholamine concentrations were also assessed at baseline and during task performance. Parallel measurements were obtained among 11 unstressed control subjects. Receptor density increased significantly between baseline and posttask measurements, but equally so in experimental and control subjects. Numbers of T suppressor/cytotoxic and natural killer cells increased selectively among subjects assigned to the experimental (stress) condition. However, there was no association between lymphocyte subset distribution and receptor density. Interindividual variability in pretask receptor density correlated significantly with heart rate and systolic blood pressure (SBP) reactivity during the initial 3 min of mental stress, but not over the entire task period. In addition, baseline receptor density correlated with SBP (but not HR) reactivity after covariance adjustment for the concomitant change in plasma catecholamine concentrations.

Adolescent↗