Pathologists' slide storage: ice age technology comes to the rescue.
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Biomedical subjects
Publications and source records attributed to A Sherwood.
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Interpretation of neurophysiological differences between control and patient groups on the basis of scalp-recorded event-related brain potentials (ERPs), although common and promising, is often complicated in the absence of information on the distinct neural generators contributing to the ERP, particularly information regarding individual differences in the generators. For example, while sensory gating differences frequently observed in patients with schizophrenia in the P50 paired-click gating paradigm are typically interpreted as reflecting group differences in generator source strength, differences in the latency and/or orientation of P50 generators may also account for observed group differences. The present study examined how variability in source strength, amplitude, or orientation affects the P50 component of the scalp-recorded ERP. In Experiment 1, simulations examined the effect of changes in source strength, orientation, or latency in superior temporal gyrus (STG) dipoles on P50 recorded at Cz. In Experiment 2, within- and between-subject variability in left and right M50 STG dipole source strength, latency, and orientation was examined in 19 subjects. Given the frequently reported differences in left and right STG anatomy and function, substantial inter-subject and inter-hemispheric variability in these parameters were expected, with important consequences for how P50 at Cz reflects brain activity from relevant generators. In Experiment 1, simulated P50 responses were computed from hypothetical left- and right-hemisphere STG generators, with latency, amplitude, and orientation of the generators varied systematically. In Experiment 2, electroencephalographic (EEG) and magnetoencephalographic (MEG) data were collected from 19 subjects. Generators were modeled from the MEG data to assess and illustrate the generator variability evaluated parametrically in Experiment 1. In Experiment 1, realistic amounts of variability in generator latency, amplitude, and orientation produced ERPs in which P50 scoring was compromised and interpretation complicated. In Experiment 2, significant within and between subject variability was observed in the left and right hemisphere STG M50 sources. Given the variability in M50 source strength, orientation, and amplitude observed here in nonpatient subjects, future studies should examine whether group differences in P50 gating ratios typically observed for patient vs. control groups are specific to a particular hemisphere, as well as whether the group differences are due to differences in dipole source strength, latency, orientation, or a combination of these parameters. Present analyses focused on P50/M50 merely as an example of the broader need to evaluate scalp phenomena in light of underlying generators. The development and widespread use of EEG/MEG source localization methods will greatly enhance the interpretation and value of EEG/MEG data.
Blunting of the normal drop in blood pressure (BP) from day to night is emerging as a strong prognostic indicator of cardiovascular morbidity and mortality. This study evaluated the effects of natural menopause on BP dipping in African American and white women. A total of 112 women (62 premenopausal and 50 postmenopausal) took part in the study. Pre- and postmenopausal groups were comparable in terms of clinic BP, body mass index, and ethnic composition. Ambulatory BP was recorded over 24 h during a typical workday, with measurements programmed to be taken every 15 min during waking hours and every 30-minutes during sleeping hours. Nocturnal BP dipping was defined as the difference between waking and sleep BP. Waking BP did not differ by menopausal status. However, nocturnal systolic BP (SBP) and diastolic BP (DBP) dipping were attenuated in postmenopausal women, with both SBP (P < .05) and DBP (P < .05) higher during nighttime sleep in postmenopausal than in premenopausal women. Ethnicity was also related to BP dipping, with African American women tending to show blunted SBP dipping (P = .055) compared with white women; BP dipping was most blunted in postmenopausal African American women. These observations suggest that blunted nighttime BP dipping may contribute to increased cardiovascular disease risk in postmenopausal women.
BACKGROUND: Postmenopausal estrogen replacement, with or without progestins, has been related to lower cardiovascular risks. OBJECTIVE: We investigated whether the actions of estrogen on vascular resistance contribute to this cardioprotective effect. DESIGN AND METHODS: In a 6-month double-blind study, pre- and post-treatment blood pressure, cardiac index, total vascular resistance index and plasma catecholamine responses during baseline and mental stressors were compared in 69 women (including 19 with mild hypertension but no history of heart disease). Women were randomized to receive either conjugated estrogens alone, estrogens plus medroxyprogesterone, or placebo. RESULTS: Both groups on active hormone replacement showed similar decreases in vascular resistance and modest blood pressure reductions, which differed from the unchanged responses of those on placebo (P< 0.05) after 3 and 6 months of treatment. Hypertensive women showed greater reductions in vascular resistance than normotensives (P< 0.05) and their blood pressure reductions tended to be larger. Women receiving hormone replacement showed increased stroke volume and cardiac index at 6 months, particularly among hypertensives and those receiving medroxyprogesterone (P < 0.05). Hormone replacement was also related to decreases in plasma norepinephrine. Finally, in 33 women receiving hormone replacement, significant 5 and 3% decreases in echocardiographic measures of left ventricular mass index and relative wall thickness were evident at 6 months (P < 0.05), while 20 placebo-treated women showed no reliable echocardiographic improvements (P= NS). CONCLUSIONS: These findings suggest that estrogen-mediated reductions in hemodynamic load on the heart may contribute to the reduced risk of cardiovascular events in relatively healthy postmenopausal women who use hormone replacement.
PURPOSE: The objective of this study was to investigate the effects of exercise training and weight loss on blood pressure (BP) associated with physical activity and emotional stress during daily life. METHODS: One hundred twelve participants with unmedicated high normal or stage 1 to stage 2 hypertension were randomized to one of three conditions: a combined exercise and behavioral weight management group (WM), an exercise-only group (EX), or a wait list control group (CON). BP was assessed in the clinic and during 15 h of daytime ambulatory BP monitoring at baseline and after 6 months of treatment. RESULTS: Increased levels of physical activity and emotional distress measured during daily life were associated with increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and rate pressure product (RPP). After treatment, the WM group had significantly lower DBP, HR, and RPP responses during both high and low levels of physical activity and emotional distress compared with the CON group. The EX group had similar BP levels as the WM group, although the EX group had significantly lower BP than the CON group during low but not high levels of physical activity and emotional distress. CONCLUSION: These findings indicate that exercise, especially when combined with weight loss, reduces BP levels at rest and in situations that typically elevate BP such as intense physical activity and emotional distress.
BACKGROUND: Lifestyle modifications have been recommended as the initial treatment strategy for lowering high blood pressure (BP). However, evidence for the efficacy of exercise and weight loss in the management of high BP remains controversial. METHODS: One hundred thirty-three sedentary, overweight men and women with unmedicated high normal BP or stage 1 to 2 hypertension were randomly assigned to aerobic exercise only; a behavioral weight management program, including exercise; or a waiting list control group. Before and following treatment, systolic and diastolic BPs were measured in the clinic, during daily life, and during exercise and mental stress testing. Hemodynamic measures and metabolic functioning also were assessed. RESULTS: Although participants in both active treatment groups exhibited significant reductions in BP relative to controls, those in the weight management group generally had larger reductions. Weight management was associated with a 7-mm Hg systolic and a 5-mm Hg diastolic clinic BP reduction, compared with a 4-mm Hg systolic and diastolic BP reduction associated with aerobic exercise; the BP for controls did not change. Participants in both treatment groups also displayed reduced peripheral resistance and increased cardiac output compared with controls, with the greatest reductions in peripheral resistance in those in the weight management group. Weight management participants also exhibited significantly lower fasting and postprandial glucose and insulin levels than participants in the other groups. CONCLUSIONS: Although exercise alone was effective in reducing BP, the addition of a behavioral weight loss program enhanced this effect. Aerobic exercise combined with weight loss is recommended for the management of elevated BP in sedentary, overweight individuals.
Emotional responsivity refers to acute changes in affective states. This study examined the relationship of emotional responsivity during daily life with ambulatory blood pressure (ABP) and psychosocial functioning. Subjects were 162 employed men and women, aged 25-45 years. Subjects underwent 24-h ABP monitoring in which they completed a behavioral diary with each cuff inflation. On a separate day, subjects completed a psychometric test battery including measures of depression, trait anxiety, and social support. Emotional Responsivity, an index of negative emotional variability during waking hours, was operationalized as the standard deviation of each individual's negative emotions scores throughout the day. Individuals with high levels of emotional responsivity showed greater increases in ABP and heart rate (HR) associated with negative emotions. Emotionally responsive individuals also reported less satisfaction with social support and higher levels of perceived daily stress, trait anxiety, and depressive symptoms. These findings suggest that psychosocial traits that have been linked to cardiovascular disease may be associated with more marked cardiovascular activation occurring in response to negative emotions experienced throughout the day.
In this investigation, the relationship between marital distress and blood pressure during daily life in a sample of married employed women was examined. It was hypothesized that greater marital distress would be associated with elevated blood pressure in the home environment, but not in the workplace. Participants were 50 married employed women, aged 25 to 45 years. Participants underwent ambulatory blood pressure monitoring on a typical workday. The women with higher levels of marital distress exhibited greater negative emotions and higher levels of blood pressure at home. These results suggest that the physiological concomitants of stress and emotional upset associated with marital distress are manifest in elevated blood pressure that is most pronounced in the home environment.
In this study, the impact of menstrual cycle phase on hemodynamic and sympathetic nervous system responses was examined during exposure to a battery of laboratory stressors. Participants were 40 healthy premenopausal women, aged 26 to 51. Impedance cardiography was used to measure stroke volume, heart rate, and cardiac output. Systemic vascular resistance was derived on the basis of concurrently recorded blood pressure and cardiac output. The menstrual cycle's effect on the sympathetic nervous system response was explored by evaluating plasma catecholamine responses during stress. In luteal compared with follicular subjects, systemic vascular resistance was significantly lower during all stress tasks (P < 0.03). Catecholamine responses were also significantly lower in luteal subjects (P < 0.004). The results suggest that the sympathetic nervous system may respond to stress differently during different phases of the menstrual cycle. This finding has implications for understanding "whitecoat hypertension" in women, and highlights the need to measure blood pressure during several office visits. Perhaps high blood pressure readings recorded during the follicular phase should be reexamined during the luteal phase before considering pharmacologic intervention.
The purpose of this study was to determine the effects of exercise and weight loss on cardiovascular responses during mental stress in mildly to moderately overweight patients with elevated blood pressure. Ninety-nine men and women with high normal or unmedicated stage 1 to stage 2 hypertension (systolic blood pressure 130 to 179 mm Hg, diastolic blood pressure 85 to 109 mm Hg) underwent a battery of mental stress tests, including simulated public speaking, anger recall interview, mirror trace, and cold pressor, before and after a 6-month treatment program. Subjects were randomly assigned to 1 of 3 treatments: (1) aerobic exercise, (2) weight management combining aerobic exercise with a behavioral weight loss program, or (3) waiting list control group. After 6 months, compared with control subjects, participants in both active treatment groups had lower levels of systolic blood pressure, diastolic blood pressure, total peripheral resistance, and heart rate at rest and during mental stress. Compared with subjects in the control group, subjects in the exercise and weight management groups also had greater resting stroke volume and cardiac output. Diastolic blood pressure was lower for the weight management group than for the exercise-only group during all mental stress tasks. These results demonstrate that exercise, particularly when combined with a weight loss program, can lower both resting and stress-induced blood pressure levels and produce a favorable hemodynamic pattern resembling that targeted for antihypertensive therapy.
BACKGROUND: Of available self-rated social phobia scales, none assesses the spectrum of fear, avoidance, and physiological symptoms, all of which are clinically important. Because of this limitation, we developed the Social Phobia Inventory (SPIN). AIMS: To establish psychometric validation of the SPIN. METHOD: Subjects from three clinical trials and two control groups were given the 17-item, self-rated SPIN. Validity was assessed against several established measures of social anxiety, global assessments of severity and improvement, and scales assessing physical health and disability. RESULTS: Good test-retest reliability, internal consistency, convergent and divergent validity were obtained. A SPIN score of 19 distinguished between social phobia subjects and controls. The SPIN was responsive to change in symptoms over time and reflected different responses to active drugs v. placebo. Factorial analysis identified five factors. CONCLUSIONS: The SPIN demonstrates solid psychometric properties and shows promise as a measurement for the screening of, and treatment response to, social phobia.
OBJECTIVE: Although hyperglycemia has been recognized as a predictor of cardiovascular autonomic neuropathy in diabetic patients, the glucose threshold at which autonomic control begins to become impaired has not been evaluated. This study examined whether fasting plasma glucose (FPG) or fasting plasma insulin (FPI) is associated with reductions in baroreflex sensitivity (BRS) in healthy volunteers. RESEARCH DESIGN AND METHODS: FPG and FPI were measured after an overnight fast in 162 healthy volunteers (91 men, 71 women) who were 25-44 years of age. BRS was measured with power spectral analysis. RESULTS: Univariate analyses showed that FPG was negatively correlated with BRS (r = -0.25, P < or = 0.001) with significant reductions observed in volunteers with FPG in the upper 2 quintiles (i.e., 93-124 mg/dl). However, after adjustment for other predictors of BRS (e.g., age, blood pressure, and BMI), the relationship between FPG and BRS was no longer significant. In contrast, FPI was negatively correlated with BRS in univariate analyses (r = -0.32, P < 0.0001) as well as after covariate adjustment, with close to a 50% reduction in BRS observed in the volunteers with insulin values in the highest quintile (i.e., 16-36 microU/ml). CONCLUSIONS: These findings suggest that high normal levels of FPG are associated with reduced autonomic control secondary to the effects of aging, obesity, and elevated blood pressure on FPG levels and that elevations in FPI are associated with substantial reductions in autonomic cardiac control independent of other covariates.
This study examined the relationship between "emotional responsivity" (i.e., individuals who exhibit relatively large variations of self-reported tension levels) and myocardial ischemia. One hundred thirty-six patients with coronary artery disease underwent 48 hr ambulatory electrocardiographic (ECG) monitoring and laboratory mental stress testing using radionuclide angiocardiography. Compared with individuals characterized as low emotional responders, a higher proportion of individuals characterized as high emotional responders exhibited wall motion abnormalities in response to laboratory mental stress testing and were more likely to exhibit ECG ST-segment depression (> or = 1 mm for > or = 1 min) during routine daily activities. These results suggest that emotional responsivity may represent an individual difference characteristic that is associated with an increased likelihood of exhibiting myocardial ischemia in both the laboratory and the real-world setting.
High cardiovascular responsivity to stressors has not consistently improved prediction of later blood pressure increases beyond the predictive effects of baseline pressure. Animal models suggest that genetic susceptibility to hypertension and frequent stress exposure are important modulating factors in stress-related hypertension. Thus in 103 men originally tested at age 18 to 22 years and reassessed 10 years later, interactive effects of genetic susceptibility (defined as 1 or more hypertensive parents) with high stress responsivity (defined as top 25% on the basis of blood pressure and cardiac responses during both reaction time and cold pressor tasks) were examined in relation to follow-up systolic and diastolic levels and to change in blood pressure status from normal (diastolic<80 mm Hg) to marginally elevated (diastolic 85 to 95 mm Hg). Men with the combination of high stress response and hypertensive parents demonstrated higher systolic (P<0.05) and diastolic levels (P<0.05) at follow-up, and they showed a 7-fold increase (7.5, 95% confidence intervals 2.3, 24.3; P<0.001) in relative risk of change in blood pressure status versus men with no family history and a 3-fold increase (3.8, confidence intervals 1.5, 9.6; P<0.004) versus less stress-responsive men who also had hypertensive parents. In 65 men who also provided ratings of daily stress, family historyxstress responsivityxdaily stress interactions were significant in predicting follow-up systolic and diastolic levels (P<0.006 and 0.03, respectively), with highest pressure levels seen when high life stress was reported by high stress responders and/or men with hypertensive parents. In conclusion, results suggest that stress responsivity as a long-term predictor is modulated by both genetic and environmental factors.
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We examined the relation of Cook and Medley Hostility (Ho) scores to alpha- and beta-adrenergic receptor responsiveness to pharmacological agonists in 22 normotensive and 14 hypertensives (aged 18-34) white males, matched for age and body mass. alpha-Adrenergic receptor responsiveness was measured by the phenylephrine dose required to increase mean blood pressure by 25 mmHg (PD25). beta-Adrenergic responsiveness was measured by the isoproterenol dose needed to increase heart rate by 25 bpm (CD25), and to lower systemic vascular resistance by 40% (VD40). Relative to men with low Ho scores (< or = 21), men with high Ho scores (> or = 21) showed significantly reduced vascular beta 2-adrenergic receptor responsiveness (VD40). Moreover, the decreased vascular responsiveness was more pronounced in borderline hypertensive men with high Ho scores. Ho scores were also marginally significant in predicting cardiac beta 1- and beta 2-adrenergic receptor responsiveness, such that men with high Ho scores showed decreased responsiveness as indexed by a larger CD25. Vascular alpha 1-adrenergic responsiveness was not associated with hostility. These observations suggest that hostility, alone or in conjunction with BP status, is associated with reduced cardiovascular beta-adrenergic receptor responsiveness.
Ambulatory blood pressure (ABP) monitoring allows frequent non-invasive blood pressure (BP) recordings in a variety of settings. Emerging evidence suggests that ABP is a better predictor of cardiovascular morbidity than clinic BP. Ambulatory blood pressure is influenced by a variety of physical, psychological and behavioral factors that comprise an individual's daily life. The present article reviews psychosocial research relating ABP to psychological factors (e.g. Type A behavior pattern, anger/hostility) and environmental influences (e.g. job strain). Psychological factors and environmental factors alone and in interaction with each other appear to substantially influence ABP. Interacting physical, psychosocial and behavioral factors that comprise daily life provide unique methodological challenges to ABP research. Methodological considerations (e.g. activity patterns, caffeine and alcohol consumption) for performing ABP research are discussed. Evidence outlined in this review suggests that psychosocial factors contribute to ABP level. To the extent that psychosocial factors contribute to ABP cardiac disease, it will be important to analyze their effects on underlying disease processes.
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