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Depression is prevalent in patients receiving hospice care. Standard antidepressant medications do not work rapidly enough in this setting. Evidence suggests that ketamine rapidly treats treatment refractory depression in the general population. Ketamine׳s role for treating depression in the hospice population warrants further study.A retrospective medical record review of 31 inpatients receiving hospice care who received ketamine for depression on a clinical basis was conducted. The primary outcome measure was the Clinical Global Impression Scale, which was used retrospectively to rate subjects׳ therapeutic improvement, global improvement, and side effects from ketamine over 21 days. Additionally, time to onset of therapeutic effect was analyzed.Using the Clinical Global Impression Scale, ketamine was found to be significantly therapeutically effective through the first week after ketamine dosing (p0.05), with 93% of patients showing positive results for days 0-3 and 80% for days 4-7 following ketamine dosing. Patients experienced global improvement during all 4 studied time periods following ketamine dosing (p0.05). Significantly more patients had either no side effects or side effects that did not significantly impair functioning at each of the 4 assessed time periods following ketamine dosing (p0.05). Additionally, significantly more patients experienced their first therapeutic response during days 0-1 following ketamine dosing (p0.001) than during any other time period.These data suggest that ketamine may be a safe, effective, and rapid treatment for clinical depression in patients receiving hospice care. Blinded, randomized, and controlled trials are required to substantiate these findings and support further clinical use of this medication in hospice settings.

Depression and anxiety are prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine has many properties that make it an interesting candidate for rapidly treating depression and anxiety in patients receiving hospice care. To test this hypothesis, a 28-day, open-label, proof-of-concept trial of daily oral ketamine administration was conducted in order to evaluate the tolerability, potential efficacy, and time to potential efficacy in treating depression and anxiety in patients receiving hospice care.In this open-label study, 14 subjects with symptoms of depression or depression mixed with anxiety warranting psychopharmacological intervention received daily oral doses of ketamine hydrochloride (0.5 mg/kg) over a 28-day period. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS), which was used to rate overall depression and anxiety symptoms at baseline, and on days 3, 7, 14, 21, and 28.Over the 28-day trial there was significant improvement in both depressive symptoms (F5,35=8.03, p=0.002, η(2)=0.534) and symptoms of anxiety (F5,35=14.275, p0.001, η(2)=0.67) for the eight subjects that completed the trial. One hundred percent of subjects completing the trial responded to ketamine for both anxiety and depression. A significant response in depressive symptoms occurred by day 14 for depression (mean Δ=3.5, d=1.14, 95% CI=1.09-5.9, p=0.01) and day 3 for anxiety (mean Δ=2.4, d=0.67, 95% CI=1.0-3.7, p=0.004). These improvements remained significant through day 28 for both depression (mean Δ=4.0, d=1.34, 95% CI=2.3-5.9, p=0.001) and anxiety (mean Δ=6.09, d=1.34, 95% CI=3.6-8.6, p0.001). Side effects were rare, the most common being diarrhea, trouble sleeping, and trouble sitting still.Patients who received daily oral ketamine experienced a robust antidepressant and anxiolytic response with few adverse events. The response rate for depression is similar to those found with IV ketamine; however, the time to response is more protracted. The findings of the potential efficacy of oral ketamine for depression and the response of anxiety symptoms are novel. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the efficacy and safety of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care or other subject populations.

Family caregivers often suffer higher levels of physical and emotional distress when caring for a chronically or terminally ill family member. Providing this kind of care to a loved one at the end of life contributes to increased stress, health problems, and a decreased quality of life. The Hospice Caregiver Support Project provided support services to caregivers identified by the hospice social worker as needing this support and/or assistance. Results from the project show that offering additional services relieved caregiver stress by allowing the caregiver time away from their caregiving role and reducing feelings of guilt and worry, and increased hospice social worker satisfaction with their ability to respond to the needs of hospice patients and caregivers.

Effective approaches to teaching attitudes, knowledge, and skills to resident physicians in primary care that can be implemented in any residency program are needed. We examined the feasibility and impact of a single palliative care residency curriculum, including a clinical rotation with a hospice program, across 5 cohorts of residents in 7 divergent primary care residency programs (both family medicine and internal medicine). The didactic content was drawn from the national Education for Physicians on End-of-Life Care Project. A total of 448 residents completed the curriculum. A large effect size was seen in measures of knowledge change (*Cohen d = .89) when compared to a national sample of primary care residency programs. Additionally, measures of confidence to perform palliative care skills and ethical concerns also improved significantly ( P < .001). A frequent comment is wishing the rest of medicine were like that experienced in the hospice setting. In a separate, ancillary evaluation, the average length of stay of patients enrolled in hospice care was 18.5 days longer for the alumni of this program when compared to physicians referring for hospice care who hadn’t experienced the curriculum.

The vast majority (80%) of care provided to hospice patients is given by informal and unpaid caregivers, who are often family members. They may be responsible for everything from management of the household and finances to medical and personal care. Providing this kind of care to a loved one at the end of life can contribute to increased stress, health problems, and decreased quality of life.Hospice social workers referred caregivers identified as needing additional support into a special project that funded services not covered by hospice and that the family could not afford to purchase. There were no restrictions on the types of services that could be requested. The Pearlin role overload measure (ROM) was administered and the family selected a service provider from an approved list of agencies. Upon completion of the service period, the ROM was re-administered. Use of the hospice respite benefit by any hospice patient during this study was compared with use before the project began.Self-reported caregiver stress, as measured by the Pearlin ROM pre- and post-services, decreased by 52% (t(122) = 10.254; p 0.0001). Use of the hospice respite benefit requested by any hospice patient caregiver decreased during the project period (χ(2), p 0.02), and when respite was requested fewer days were used as compared with the same time period prior to the project (χ(2), p 0.0043).The project results show that offering such services relieved caregiver stress, reduced use of respite, and reduced the number of respite days used.

To investigate whether an association exists between experiences of everyday discrimination and blood pressure (BP) dipping in a biracial sample of black and white adults. Attenuated nocturnal BP dipping is closely linked to cardiovascular morbidity and mortality. Self-reported experiences of everyday discrimination have also been associated with negative cardiovascular health outcomes.Seventy-eight hypertensive and normotensive women and men (n = 30 black and 48 white) reported on their experiences of everyday discrimination (Everyday Discrimination Scale) and underwent two separate 24-hour ambulatory BP monitoring (ABPM) sessions approximately 1 week apart.Correlation analysis revealed that higher endorsement of everyday discrimination was significantly associated with less diastolic BP (DBP) and systolic BP (SBP) dipping (p.05). Subsequent hierarchical regression analyses indicated that everyday discrimination explained 8% to 11% of the variance in SBP and DBP dipping above and beyond other demographic and life-style-related factors, including race, age, 24-hour BP, body mass index, and current socioeconomic status. The relationship between discrimination and dipping was significantly stronger on the second night of monitoring. Finally, analyses revealed that everyday discrimination mediated the relationship between race and BP dipping.These findings suggest that experiences of everyday discrimination are associated with less nocturnal SBP and DBP dipping above and beyond the effect of known covariates. The use of multiple ABPM sessions may facilitate the detection of relationships between psychological variables and BP dipping.

This study examined chronic and short-term stress effects on heart rate variability (HRV), comparing time, frequency and phase domain (complexity) measures in 50 healthy adults. The hassles frequency subscale of the combined hassles and uplifts scale (CHUS) was used to measure chronic stress. Short-term stressor reactivity was assessed with a speech task. HRV measures were determined via surface electrocardiogram (ECG). Because respiration rate decreased during the speech task (p < .001), this study assessed the influence of respiration rate changes on the effects of interest. A series of repeated-measures analyses of covariance (ANCOVA) with Bonferroni adjustment revealed that short-term stress decreased HR D2 (calculated via the pointwise correlation dimension PD2) (p < .001), but increased HR mean (p < .001), standard deviation of R–R (SDRR) intervals (p < .001), low (LF) (p < .001) and high frequency band power (HF) (p = .009). Respiratory sinus arrhythmia (RSA) and LF/HF ratio did not change under short-term stress. Partial correlation adjusting for respiration rate showed that HR D2 was associated with chronic stress (r = −.35, p = .019). Differential effects of chronic and short-term stress were observed on several HRV measures. HR D2 decreased under both stress conditions reflecting lowered functionality of the cardiac pacemaker. The results confirm the importance of complexity metrics in modern stress research on HRV.

Summary Introduction Recent evidence implicates a cholinergic anti-inflammatory pathway. Because vagus nerve activity mediates some heart rate variability (HRV), this qualitative review examines the literature concerning circulating cytokines and HRV in cardiovascular function in humans. This qualitative review examines the literature concerning circulating cytokines and HRV in cardiovascular function in humans. Methods Thirteen studies on HRV, inflammation, and cardiovascular function were located by electronic library search and descriptively reviewed. Results The relationship between HRV and inflammation was studied in healthy controls, patients with acute or stable coronary heart disease (CHD), patients with metabolic syndrome or impaired glucose tolerance and patients with kidney failure. Investigations focused mainly on Interleukin-6 (IL-6) and C-reactive peptide (CRP). The majority of reviewed studies reported that parasympathetic nervous system tone as inferred from heart rate variability is inversely related to inflammatory markers ( r values between −0.2 and −0.4). The relationships with inflammatory markers were similar whether derived from ECG signals as short as 5–30 min or from 24-h ECG readings for HRV analyses. While inflammatory markers appear to be related to HRV, it is a mistake to assume that the traditional “vagal measures” of HRV (such as high frequency heart rate variability) are the driving factors. Indeed, low frequency heart rate variability, a complex measure reflecting both parasympathetic and sympathetic activity, is the more commonly associated measure linked to inflammatory markers. Discussion Heart rate variability is inversely correlated with inflammatory markers in healthy individuals as well as in those with cardiovascular diseases.

Decreased heart rate variability (HRV) has been associated with an increased risk of atherosclerosis. We hypothesized that a decrease in frequency domains of resting HRV would be associated with elevated plasma levels of interleukin (IL)-6 and soluble tissue factor (sTF) both previously shown to prospectively predict atherothrombotic events in healthy subjects. Subjects were 102 healthy and unmedicated black and white middle-aged men and women. We determined IL-6 and sTF antigen in plasma and HRV measures from surface electrocardiogram data using spectral analysis. All statistical analyses controlled for age, gender, ethnicity, smoking status, blood pressure, and body mass index. Low amounts of low frequency (LF) power (beta=-0.31, p=0.007) and high frequency (HF) power (beta=-0.36, p=0.002) were associated with increased amounts of IL-6, explaining 7% and 9% of the variance, respectively. Interactions between LF power and IL-6 (p=0.002) and between HF power and IL-6 (p=0.012) explained 8% and 5%, respectively, of the variance in sTF. Post hoc analyses showed associations between IL-6 and sTF when LF power (beta=0.51, p

Objective: Hypertension is more frequent and more severe in older individuals and in African Americans. Differences in autonomic nervous system activity might contribute to these differences. Autonomic effects on the heart can be studied noninvasively through analysis of heart rate variability (HRV). We examined the effects of age and ethnicity on HRV. Methods: We studied 135 subjects (57 African Americans and 78 Caucasian Americans), aged 23 to 54 years. Using their surface electrocardiogram (ECG) data, we calculated the HRV indices with spectral analyses. High frequency (HF) power was used to index parasympathetic activity, whereas the ratio of low to high frequency power (LF/HF) was used to index sympathovagal balance. Results: Three HRV indices (HF, LF power, and LF/HF) were significantly related to age in Caucasian Americans but not in African Americans. The effect of age, ethnicity, and the age-by-ethnicity interaction on HF and LF power was significant, even after controlling for gender, body mass index, and blood pressure. Conclusions: Young African Americans manifested a pattern of HRV response similarly to older Caucasian Americans. These results suggest that young African American individuals might show signs of premature aging in their autonomic nervous system.

Obstructive sleep apnea (OSA) is associated with recurrent episodes of nocturnal hypoxia and increased risk for development of systemic hypertension. Prior studies have been limited, however, in their ability to show reduction in blood pressure after continuous positive airway pressure (CPAP) therapy, and the effect of supplemental oxygen alone on blood pressure in OSA has not been evaluated. We performed a randomized, double-blind, placebo-controlled study comparing the effects of 2 weeks of CPAP versus sham-CPAP versus supplemental nocturnal oxygen on 24-hour ambulatory blood pressure in 46 patients with moderate-severe OSA. We found that 2 weeks of CPAP therapy resulted in a significant reduction in daytime mean arterial and diastolic blood pressure and nighttime systolic, mean, and diastolic blood pressure (all P s

OBJECTIVE: The deleterious effects of major depressive disorder on cardiovascular (CV) functioning are well known. However, the etiologic mechanisms underlying this association are incompletely understood. In the current study, subjects with varying degrees of depressive symptoms performed a stress task while CV reactivity was measured. We hypothesized that high levels of depressive symptoms would be associated with altered CV reactivity. METHODS: Ninety-one healthy volunteer subjects performed reactivity testing while measures of impedance cardiography and autonomic nervous system function were obtained. Subjects completed the Center for Epidemiological Studies Depression Scale (CES-D) and were categorized into either the high depressive (i.e., CES-D > or =16) or low depressive (i.e., CES-D

OBJECTIVES To investigate the relationship between sleep quality and nocturnal blood pressure dipping in normal subjects. We hypothesized that sleep quality correlates with dipping. DESIGN Cross-sectional study. SETTING Unattended polysomnography in the home followed by a 24-hour ambulatory blood pressure measurement. PATIENTS Eighty-eight self-described normal subjects were evaluated; 26 were excluded due to an apnea-hypopnea index > or = 10. None were taking antihypertensive medications. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Subjects were divided into dippers and nondippers based on > or = 10% drop in nocturnal mean arterial pressure (MAP). Sleep-quality variables included total sleep time; sleep latency; percentage of stages 1, 2, 3, 4, and rapid-eye-movement sleep; percentage of wake time after sleep onset (WASO); total arousal index; and sleep efficiency. Of the remaining 62 subjects, 17.7% were nondippers, and 7 were hypertensive. There was no difference in age, body mass index, apnea-hypopnea index, blood pressure, or sleep quality between groups. Stage 4 sleep correlated significantly with dipping of diastolic blood pressure and MAP (r = 0.410 and 0.378, respectively, P < or = .002), and percentage of WASO was negatively correlated with dipping of diastolic blood pressure (r = -0.360, P = .004), suggesting that greater dipping was associated with better sleep quality. On multivariate analyses, Stage 4 sleep was independently associated with dipping of diastolic blood pressure (P = .034) after adjusting for screening MAP, percentage of WASO, total arousal index, and Stage 1 sleep. The same link was found between Stage 4 sleep and dipping of MAP (P = .05) after adjusting for screening MAP, age, sex, and body mass index. Repeat analyses excluding hypertensives yielded similar findings. CONCLUSION Our data suggest that deeper and less-fragmented sleep is associated with more blood pressure dipping in normal subjects.

The anterior cingulate cortex (ACC) has diverse functions and several functional subdivisions. This study implemented a counting Stroop task that presented incongruent (INC) and congruent (CON) stimuli at two speeds to probe dorsal (dACC) and ventral (vACC) using functional magnetic resonance imaging (fMRI). Eighteen healthy subjects completed the task twice: once outside the scanner while heart rate variability (HRV) was recorded and once during fMRI. In both sessions, subjects completed two runs. Stimuli were presented every 2.0 s in one run and every 1.5 s in the other. fMRI data analysis revealed two important findings. First, by computing differential activation between INC and CON stimuli, a cluster of activation related to response inhibition was observed in the left dACC. Additionally, by calculating the interaction of speed with stimulus congruency, a cluster of activation was observed in the left vACC. This activation correlated significantly with high-frequency HRV (P < 0.02 for CON and P < 0.003 for INC) and represents the parasympathetic modulatory role of the vACC. This study supports the notion of functional subdivisions within the ACC and links the processes of cognitive interference and parasympathetic modulation with activation in specific subregions of the ACC, a structure that is critical for the interface between cognition and emotion.

To examine the effects of regular physical activity on lymphocyte responses to a speech stressor and an exercise challenge.We assessed lymphocyte subsets and CD62L expression pre, immediately after and 15 min after a speech task vs. exercise in 24 high vs. 24 low physically active subjects. Catecholamine levels were determined by radioenzymatic assay, and enumeration of cells was assessed by flow cytometry.Both tasks induced significant increases in plasma epinephrine (EPI; P.05) and norepinephrine (NE; P.001) levels. Similarly, both tasks led to increases in the numbers of lymphocyte subsets (P.05). Physically active individuals showed attenuated responses to the speech stressor in numbers of CD62L(+), CD45RA(+), CD45RO(+) CD8(+), CD45RO(+) T(H) and CD62L(-) natural killer (NK) cells (P's.05). In contrast, physical activity level had no significant effect on lymphocyte subsets or CD62L expression in response to exercise.The findings suggest that physical fitness affects immune responses to a psychological but not a physical stressor. It is an interesting but open question whether attenuated lymphocyte trafficking responses to stress in regular exercisers might have clinical implications regarding host defense by the immune system.

Cardiovascular disease is the leading killer of women in developed countries. Menopause, stress, and lack of social support may contribute to the increased risk of heart disease morbidity and mortality in women. This study examined the effects of psychological stress and social support on autonomic nervous system control of the heart in 18 pre- and 34 postmenopausal women. Autonomic activity, as indexed by high-frequency heart rate variability and pre-ejection period, was assessed at rest and during a public speech task. Social support was determined using the Berkman Social Support Inventory. Postmenopausal women had higher heart rate (F = 4.4, p pound.04) and less parasympathetic activity (F = 11.9, p pound.001) compared with premenopausal women at rest. In response to stress, sympathetic nervous system activity increased in postmemopausal women (F = 6.1, p pound.02); however, this effect was no longer significant when age was used as a covariate in the analysis. Social support did not significantly affect measures of autonomic activity in either the pre- or postmenopausal women. Postmenopausal women have greater sympathetic and less parasympathetic activity than premenopausal women, which may account for their increased risk of coronary artery disease.

BACKGROUND Non-invasive continuous blood pressure monitoring has, for the past decade, been performed using the Finapres monitor. Radial tonometry is a new methodology for measuring non-invasive beat-to-beat blood pressure. This technique has been evaluated for other applications, but its use in cardiovascular reactivity testing has not yet been reported. DESIGN A convenience sample was used to compare a radial tonometric device (Colin Pilot) with intermittent brachial blood pressure measurement (Critikon Dinamap) during reactivity testing. A second comparison was made between an Ohmeda Finapres and a Dinamap. METHODS Twenty subject-testing sessions during a reactivity protocol were evaluated for blood pressure determination. Separate groups of subjects were used for Pilot versus Dinamap comparisons and Finapres versus Dinamap comparisons. Blood pressure signals from 15 subjects with Pilot and 15 subjects with Finapres data were evaluated for artifacts. Signals were also compared in a subject with Raynaud's phenomenon. RESULTS Both devices tracked blood pressure well. The Finapres significantly overestimated systolic blood pressure ( P < 0.001). The correlations between the Pilot and Dinamap were consistently higher than those between the Finapres and Dinamap. There were more artifacts (3.2%) with the Finapres than with the Pilot (0.2%). In the subject with Raynaud's phenomenon, the Finapres overestimated blood pressure by more than 40 mmHg and showed more than 75% of artifacts. On the other hand, the Pilot tracked blood pressure in the same subject without error. CONCLUSIONS Radial tonometric continuous beat-to-beat blood pressure monitoring with the Colin Pilot was associated with a low artifact rating and high accuracy of blood pressure measurement during reactivity testing.

This study examined the effects of acute psychological stress on lymphocyte subsets and their differential changes according to their cell adhesion molecule expression in cardiac versus vascular reactors. We classified 49 subjects into cardiac or vascular reactors based on the participants' cardiac output or total peripheral resistance reactivity to a speech presentation task. Analysis demonstrated that there were no significant differences in lymphocyte counts or adhesion molecule expression between cardiac and vascular reactors at rest. Cardiac reactors showed a significant decrease of surface density of CD62L on mixed lymphocytes (p.001) as well as on CD4 (p.01) and CD8 T-cells (p.001). There was also a disproportionate increase in the number of CD62L(-) T cells compared to CD62L(+) T cells only in cardiac reactors (p.001). There were no significant effects of the stressor observed in vascular responders. The findings replicate previous studies demonstrating associations between cardiovascular and immune responses to acute stress and extends those findings by suggesting that the relationship is more significant in individuals who increase their blood pressure primarily through a cardiac mechanism.

Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age 6 SD, 40 6 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI0,120). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r 5 .43, P 5 .005). There were time effects for all variables of interest. While vWF antigen (P 5 .044), epinephrine (P 5 .003), and diastolic BP (P 5 .001) decreased after glucose challenge, norepinephrine (P 5 .009), systolic BP (P 5 .022), and heart rate (P < .001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r 5 .46, P 5 .004) and with screening systolic BP (r 5 .45, P 5 .004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI0,120. The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance. Copyright © 2001 by W.B. Saunders Company

OBJECTIVE Obstructive sleep apnea (OSA) is associated with increased prevalence of atherosclerotic disease. A hypercoagulable state thought to underly atherosclerosis has been described in both OSA and systemic hypertension. We wondered about the respective contribution of apnea and hypertension to a hypercoagulable state. DESIGN Eighty-seven subjects with symptoms suggestive of OSA, mean age 47 years (range 32-64 years), underwent polysomnography and blood pressure (BP) screening. OSA was diagnosed when respiratory disturbance index (RDI) > or = 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP (DBP) > 90 mmHg were classified as having hypertension. Three hypercoagulability markers were measured: thrombin/antithrombin III complex (TAT), fibrin D-dimer (DD), and von Willebrand factor antigen (vWF:ag). RESULTS Analysis of variance and multiple linear regression were performed on the following four subject groups: (1) normotensive non-apneics (n = 19), (2) normotensive apneics (n = 38), (3) hypertensive non-apneics (n = 11), and (4) hypertensive apneics (n = 19). OSA (groups 2 and 4) had no significant main effect on hemostasis. Hypertensives (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range, 148/59-188 versus 77/53-108 pmol/l; P = 0.009) and of DD (376/265-721 versus 303/190-490 ng/ml; P = 0.040) than normotensives (groups 1 and 2). Across all subjects, SBP was the only significant predictor of TAT (P = 0.001) and of DD (P = 0.004), whereas DBP was the only significant predictor of vWF:ag (P = 0.029). These findings persisted even after controlling for gender, age, body mass index, RDI, mean SaO2, and hematocrit. CONCLUSION Hypercoagulability in OSA is mediated by comorbid hypertension and might account for high cardiovascular morbidity in OSA in general.

Epinephrine (E) infusions raise blood pressure and there is an excess incidence of hypertension among males and blacks. However, reports of E levels by ethnicity, gender, and blood pressure status are inconsistent. Insensitive assays, variability in plasma E levels within individuals, and the small size of most studies have contributed to these conflicting reports. We measured plasma E levels in a large diverse sample of subjects, using a highly sensitive assay. A total of 361 individuals participated in the study: 61% were men and 39% women, 74% were normotensive and 26% hypertensive, 59% were white and 41% were black. Except for difference in blood pressure and body mass index between the normotensives and hypertensives, subjects had similar baseline characteristics and took no antihypertensive medications for at least five days prior to sampling. All blood samples were collected after resting for a least 30 minutes following the insertion of an indwelling i.v. catheter. Catecholamine levels were determined using a radioenzymatic assay (assay sensitivities for E and norepinephrine were 6 pg/ml and 10 pg/ml, respectively). An ethnicity by gender interaction was found (F(1,315) = 5.126, p = .024). Subsequent analysis revealed that white women had significantly lower basal plasma E levels than white men (p0.001) and black women (p = 0.036). There were no significant differences in E levels between black men and women or between white men and black men. Uncorrected E levels were lower in normotensive than hypertensive subjects (p = .009) but this difference was not significant when corrected for body mass index (BMI). Uncorrected norepinephrine levels were higher in women than men (p = .03) but the difference was no longer significant when corrected for BMI. Plasma E levels were significantly lower among white women than men or black women. In contrast to prior studies, E levels were lower in hypertensives, but this may reflect obesity among hypertensives.

The need for doctors who have skills in pain management and palliative medicine is greatest in low and moderate resource countries where patients most frequently present to their health care system with advanced illness and greater than 80% of the global deaths occur. While medical students trained in the United States are required to have training in palliative medicine, international medical graduates (IMGs), who have completed medical school outside North America, may not have the same exposure to palliative medicine training as U.S. physicians. The goal of this study was to evaluate whether a four-week course in palliative medicine could bring IMG attitudes, concerns, competence, and knowledge to the level of U.S. trainees.As part of a prospective cohort study, 21 IMGs from 14 countries participated in a four-week course in palliative medicine. Attitudes, concerns, self-reported competence, and knowledge were assessed pre-course and post-course. The course was evaluated weekly and at the end of the four-week program. The data from the IMGs was compared to data from U.S. medical students and residents using the same assessment tools.After the course, IMGs had significantly decreased concern about ethical and legal issues in palliative medicine to the level of U.S.-trained residents and a significant increase in knowledge and self-rated competence equivalent to the level of U.S. trainees.A four-week course in palliative medicine can improve the levels of concern, knowledge and self-assessed competence in IMGs to the level of US trainees.

Community physicians are often ill-prepared for the management of complex symptoms. With a shortage of board certified physicians in palliative medicine to assist, the result is a lack of access to critical pain and symptom management expertise to care for seriously ill Californians. We report on a palliative medicine telephone hotline available to health care professionals.San Diego Hospice and The Institute for Palliative Medicine received a grant to provide a telephone hotline for health care professionals to assist in answering clinical questions relating to palliative care. An extensive marketing campaign was initiated to publicize the service. Information from the calls was collected over a 2.5-year period. The data included referral source, geographic area, diagnosis, and reason for call. Satisfaction surveys were sent following each call.During the first 2.5 years of operation 498 calls were recorded. Although marketing was directed within the state of California, the majority of calls originated outside the state after the first year (66%). Approximately 43% of calls came from physicians, followed by 22% from registered nurses, 15% from nurse practitioners, and 6% from pharmacists. Nearly half of the calls were received from repeat callers. The most frequent topics for callers were related to pain and symptom management (29%), followed by hospice care (21%), medication dosing, and general palliative care (14% each). Ninety-five percent of the callers completed the satisfaction survey with 89% likely to use the service again.The hotline proved to be a valuable resource for health care providers caring for patients requiring palliative care as evidenced by the steady increase in the number of calls over the initial 2.5 years of operation. Future research on how the information directly impacted patient care might generate data to support the continuation of this service via partnerships with other organizations.

To evaluate the effects of race and gender on recovery, i.e. the relative return to baseline after a stress challenge, cardiovascular and catecholamine measures were examined before, during and after two standardized laboratory stressors (a speaking and a mirror tracing task) in a group of 85 Black and White men and women (mean age 35.6 years, range 20 to 52). For the speech task, White men showed the least systolic (p0.025) and diastolic (p0.05) blood pressure recovery as compared to Black men and women. For the mirror star tracing task, total peripheral resistance (p0.03) recovery was least for Whites as compared to Blacks and heart rate (p0.04) recovery was least for White women as compared to Black women and men. There were no significant group effects in terms of catecholamine recovery from either task. The findings extend prior studies on race and gender by suggesting that these same characteristics affect recovery from stressors.

Objective To examine possible effects of race, sex, and the menstrual cycle on adrenergic receptors (β2 and α2) and agonists. Methods Sixty-three normotensive black men and women and white men and women were studied twice, approximately 6 weeks apart. Women were studied once during the follicular phase and once during the luteal phase of the menstrual cycle. β2-Adrenergic receptors and adenylate cyclase activity were examined on lymphocytes, and α2-adrenergic receptors were examined on platelets. Norepinephrine and epinephrine were determined in plasma. Results Women showed greater lymphocyte β2-receptor sensitivity (isoproterenol-stimulated cyclic adenosine monophosphate; p = 0.009). Women also showed greater postreceptor adenylate cycle activity independent of the β-receptor (forskolin stimulation; p = 0.006). When these differences were controlled for, the gender-related differences in β2-receptor sensitivity were no longer evident. Black women had a reduced β2-receptor sensitivity in the luteal phase compared with the follicular phase, whereas white women showed no significant change (p = 0.018). Black subjects had lower lymphocyte β2-receptor density (Bmax) values than white subjects (p = 0.047). There were no significant effects on α2-adrenergic receptors. Conclusion The findings suggest that although there is no generalized effect of the menstrual cycle on adrenergic receptors in white women, such an effect may occur in black women. The findings also suggest that previously reported gender-related differences in β2-receptor sensitivity may be due to gender-related differences in postreceptor activity and not the β2-receptor per se. Clinical Pharmacology & Therapeutics (1996) 60, 99–104; doi

Abstract This study examined cardiovascular and catecholamine responses to two standardized laboratory stressors in 33 healthy age- and weight-matched black and white normotensive women (mean age, 32 years) during two phases of the menstrual cycle. Subjects were studied in a randomized order at the same time of day on two separate occasions approximately 6 weeks apart, once during the follicular phase (days 7 to 10 after menses) and once during the luteal phase (days 7 to 10 after the leutenizing hormone surge) of the menstrual cycle. Black women had higher systolic ( P =.01) and diastolic ( P =.01) pressures compared with white women. Black women showed greater diastolic pressure ( P P

This study examined relationships between psychologic characteristics and enumerative immune responses to an acute laboratory stressor. Lymphocyte subsets were measured in 104 subjects at rest and following a 6-minute laboratory naturalistic speaking stressor. Multiple linear regression was utilized to assess relationships between immune reactivity (change scores) and anger expression, hostility, anxiety, depression, and stress. The task resulted in significant increases over baseline in WBC (p < 0.001), T-suppressor/cytotoxic CD8 cells (p = 0.010) natural killer CD56 cells (p < 0.0001), and CD57 (p < 0.0001) cells, and significant decreases in T-cells (p = 0.012), T-helper cells (p = 0.003), B-cells (p < 0.001), and the T-helper/suppressor ratio (p < 0.001). In general, the regression suggested that moderate associations exist between certain psychologic attributes and acute subset redistribution. For example, the increase in natural killer cell subsets was significantly negatively associated with anger expression, hostility, and depression. Suppressor/cytotoxic (CD8) cell reactivity was associated with baseline as well as with the task-induced changes in anxiety. B-cell (CD19) responses were related to the subject's age, expression of anger, and depression scores. As with the cardiovascular reactivity literature, these findings suggest that a relationship exists between certain psychologic characteristics such as anger and anxiety and immune reactivity to acute stress.

To the Editor: The hot flash is one of the most commonly encountered symptoms of menopause, yet there is little understanding of its underlying physiology. With its unpredictable onset and evanesce...

This study examined demographic and adrenergic characteristics associated with enumerative immune responses to acute laboratory stress. Lymphocyte subsets and plasma catecholamines were measured in 110 subjects at rest and following a naturalistic speaking stressor. Lymphocyte β2-adrenergic receptor sensitivity and density were measured at rest. The speaking task caused marked increase in natural killer cells, T-suppressor/cytotoxic cells, total WBC, norepinephrine, and epinephrine and decreases in T-helper cells, B cells, and the T-helper/suppressor ratio. Multiple regression analyses demonstrated that, in general, cellular immune responses were best predicted by a combination of lower basal norepinephrine, higher β2-adrenergic receptor sensitivity, and a greater stress-induced increase in norepinephrine. The findings suggest that traditional epidemiologic characteristics such as gender, ethnicity, and mild hypertension have limited influence on lymphocytosis. Rather, interindividual differences in sympathetic nervous system characteristics play a more prominent underlying role in acute cellular immune system activation.

This study examined the relationship between sleep apnea and beta 2-adrenergic receptor characteristics. Using standard polysomnography, individuals were classified as either apneic (n = 15) or mild to nonapneic (n = 15) according to their respiratory disturbance index (RDI). Subjects were similar in terms of sodium excretion and blood pressure. Apneic subjects showed a decrease in beta 2-adrenergic receptor sensitivity (p = 0.01) [as determined by isoproterenol-stimulated cyclic adenosine 5'-monophosphate (AMP) production in lymphocytes] and an increased binding affinity to the beta receptor antagonist [125I]iodopindolol (p < 0.001). beta receptor density was also diminished in apneics, but not significantly (p = 0.08). Forskolin-stimulated cyclic AMP was not significantly different between the groups, indicating a similarity in postreceptor Gs-adenylate cyclase activation. Across all subjects, RDI was negatively correlated with beta receptor sensitivity (r = -0.35, p = 0.05) and Kd (r = -0.54, p < 0.01) and positively correlated with systolic blood pressure (r = 0.37, p < 0.05). The findings indicate that sleep apnea is associated with a diminished beta 2-adrenergic receptor function but no change in postreceptor components and suggest a mechanism for the high comorbidity between sleep apnea and hypertension.

Abstract This study examined the effects of ethnicity and hypertension on β 2 -adrenergic receptors and on plasma catecholamines in a group of 77 unmedicated mildly hypertensive and normotensive men. Black hypertensive subjects had the most sensitive and white hypertensive subjects the least sensitive β-receptors (as assessed by isoproterenol-stimulated cyclic AMP in lymphocytes [ P =.02]). In contrast, postreceptor adenylate cyclase activation (as assessed by forskolin stimulation) was similar among groups. As with β-receptor sensitivity, black hypertensive subjects had the highest β-receptor density and white hypertensive subjects the lowest ( P =.03). Blacks demonstrated lower plasma epinephrine values compared with whites ( P =.03). Across all subjects, plasma epinephrine was negatively correlated with β-receptor density ( r =−.26, P r =−.25, P

Insulin is a modulator of blood pressure and may play a role in the pathogenesis of hypertension. This study examined the relationship between fasting insulin level and cardiovascular reactivity in hypertensive and normotensive black and white patients. Eighty-one patients were studied after 3 days of hospitalization on an isocaloric diet providing 200 mmol Na+ and 100 mmol K+ per day. Fasting insulin levels were determined on the morning of the second hospital day; a median split was used to determine high- and low-insulin groups. On the next day of hospitalization we examined blood pressure and hemodynamic responses to a speaking challenge. Hemodynamic responses were determined with impedance cardiography. Reactivity was studied as the percentage change from resting baseline. There were significant race by blood pressure level interactions for systolic and diastolic blood pressure reactivity (P < or = .01). Black hypertensives showed more blood pressure reactivity than either the white hypertensives or the white normotensives; black normotensives had less blood pressure reactivity than the other groups. Insulin grouping interacted with blood pressure level and race on the reactivity of the underlying hemodynamic measures (total peripheral resistance, stroke volume, and heart rate; P < or = .02). Fasting insulin level had no relationship to blood pressure reactivity. On the other hand, insulin level interacted with blood pressure level and race on the underlying hemodynamics controlling blood pressure, namely total peripheral resistance and stroke volume.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the impact, retention, and magnitude of effect of a required didactic and experiential palliative care curriculum on third-year medical students' knowledge, confidence, and concerns about end-of-life care, over time and in comparison to benchmark data from a national study of internal medicine residents and faculty.Prospective study of third-year medical students prior to and immediately after course completion, with a follow-up assessment in the fourth year, and in comparison to benchmark data from a large national study.Internal Medicine Clerkship in a public accredited medical school.Five hundred ninety-three third-year medical students, from July 2002 to December 2007.Pre- and postinstruction performance on: knowledge, confidence (self-assessed competence), and concerns (attitudes) about end-of-life care measures, validated in a national study of internal medicine residents and faculty. Medical student's reflective written comments were qualitatively assessed.Required 32-hour didactic and experiential curriculum, including home hospice visits and inpatient hospice care, with content drawn from the AMA-sponsored Education for Physicians on End-of-life Care (EPEC) Project.Analysis of 487 paired t tests shows significant improvements, with 23% improvement in knowledge (F(1,486)=881, p0.001), 56% improvement in self-reported competence (F(1,486)=2,804, p0.001), and 29% decrease in self-reported concern (F(1,486)=208, p0.001). Retesting medical students in the fourth year showed a further 5% increase in confidence (p0.0002), 13% increase in allaying concerns (p0.0001), but a 6% drop in knowledge. The curriculum's effect size on M3 students' knowledge (0.56) exceeded that of a national cross-sectional study comparing residents at progressive training levels (0.18) Themes identified in students' reflective comments included perceived relevance, humanism, and effectiveness of methods used to teach and assess palliative care education.We conclude that required structured didactic and experiential palliative care during the clinical clerkship year of medical student education shows significant and largely sustained effects indicating students are better prepared than a national sample of residents and attending physicians.

While the importance of receptor-mediated intracellular cyclic AMP in blood pressure regulation is well documented, few studies have evaluated the physiologic relevance of cyclic AMP exported from cells. We report evidence of a relationship between blood pressure and the transport of intracellular cyclic AMP from lymphocytes. Twenty-eight hypertensive and 56 normotensive white and black volunteers (mean age 40 years) were studied. Both intra- and extracellular concentrations of cyclic AMP were determined in lymphocytes following incubation with 10(-5) M isoproterenol. Compared to normotensives, hypertensives (p = 0.001), particularly white hypertensives (p = 0.023) had higher levels of exported cyclic AMP. These values were independent of intracellular concentrations of cyclic AMP, which were similar across the groups. Exported cyclic AMP was independent of both sodium excretion and beta-adrenergic receptor sensitivity, the latter being lower in white hypertensives (p = 0.024). Across all subjects, exported cyclic AMP was correlated with MAP (r = .39, p0.001). These findings indicate that the active transport of cyclic AMP may be enhanced in hypertension and suggest a possible pathway which might explain existing data of increased cyclic AMP levels in hypertension.

Objectives To assess the educational offerings provided to psychiatry residents in palliative care as well as their concomitant interest in learning more about this subspecialty. To measure the pre- and post-levels of competence, concern, and knowledge exhibited by psychiatry residents when completing a formalized clinical rotation in hospice and palliative care, with additional comparisons to family and internal medicine residents completing the same clinical rotation. Methods Fifty-two Psychiatry Program Directors and 98 psychiatry residents completed an online survey assessing the current course offerings and level of interest in palliative care. Thirty psychiatry residents were additionally evaluated before and after completion of a clinical rotation in hospice and palliative care. Results Few programs offered any formalized training in palliative care, although nearly all psychiatry residents reported interest in this area. A clinical rotation in palliative care significantly increased psychiatry residents' competence and knowledge while simultaneously decreasing their concerns about practice in this area; most were at levels comparable to family and internal medicine residents completing the same rotation. Psychiatry residents' knowledge of pain assessment, pain management, and generalized non-pain management were also enhanced during the rotation. Conclusions Results indicate that training opportunities in palliative care are lacking for psychiatry residents in the United States although residents report strong interest in this area. This study finds psychiatry residents can benefit as much as other disciplines from receiving palliative care training. The need to offer such training within psychiatry residencies is highlighted and the welcoming of psychiatrists into palliative care is suggested.

In cardiovascular reactivity studies, interpretations of the processes supporting the blood pressure response may become problematic when systolic blood pressure, diastolic blood pressure, and heart rate all increase in response to a behavioral challenge. Therefore, in addition to evaluating these cardiovascular responses, this study examined cardiac output, total peripheral resistance and systolic time intervals derived from impedance cardiogram, electrocardiogram and phonocardiogram recordings during a speech stressor, a mirror tracing task, and a foot cold pressor test. All of the behavioral stressors elicited increases in blood pressure and heart rate, with the largest changes occurring during the overt speech. Based on the examination of the response patterns of the underlying hemodynamic variables it would appear that, in both men and women, the blood pressure increase during the speech preparation period was supported by increased cardiac output; the speech itself resulted in a mixed pattern of increased cardiac output and total peripheral resistance; whereas, the mirror tracing and cold pressor tasks produced increased total peripheral resistance. Although men and women produced similar response patterns to the behavioral challenges, sex differences in the estimates of myocardial contractility were observed during rest. These results provide evidence that different behavioral stressors can produce a distinct yet integrated pattern of responses, whose differences may be revealed, when impedance cardiography is used, to derive sufficient response measures for assessing dynamic cardiovascular processes.

BACKGROUND Atrial natriuretic peptide (ANP) is a hormonal regulator of cardiovascular fluid volume. More than 1,000 scientific articles were written about ANP between 1987 and 1991. Because some articles hinted at problems with storing ANP, this study examined the effect of numerous techniques for storing and processing human ANP samples. METHODS AND RESULTS Samples were obtained repeatedly from three patients, treated, and stored under a variety of conditions. Experiment 1 evaluated the effects of different preservatives at 35, 21, 14, 10, and 7 days before assay. Experiment 2 evaluated nonspecific binding of ANP to different storage tubes during 28 days of storage. Experiment 3 evaluated the effect of storage at -20 degrees C, -80 degrees C, and -196 degrees C for 1 month. ANP was very unstable, degrading as much as 30% after 3 days of storage and by more than 50% in 1 month even when stored at -80 degrees C. Only storage at -196 degrees C (in liquid nitrogen) kept ANP stable for 1 month. Extraction and lyophilization of the samples before freezing and assay within 7 days of freezing only partially minimized the amount of degradation. All other processing techniques had little effect on slowing the degradation of ANP. CONCLUSIONS These findings raise disturbing questions about the interpretation of the substantial literature on ANP.

Although neighborhood disadvantage has been linked to the development of cardiovascular disease, the mechanism through which living in impoverished neighborhoods is associated with poor cardiovascular health is not well understood. Additionally, it is not clear whether individual socioeconomic status (SES) interacts with neighborhood factors to influence cardiovascular outcomes. Using multilevel modeling, we examined the interaction between neighborhood poverty and individual SES on pressor responses to an alpha agonist, Phenylephrine (PE), in an adult sample of 105 African-Americans and 106 Caucasian-Americans. Neighborhood poverty was assessed using census block data gathered from the Census Bureau. Education and occupation were used to assess individual SES. Pressor responsiveness was calculated as the systolic and diastolic blood pressure (BP) response to a 100-microgram PE bolus administered intravenously. There was a significant interaction between education and neighborhood poverty on pressor responses. Higher education was associated with smaller BP responses to PE; but only in individuals who lived in neighborhoods in which less than 5% of the residents lived below the poverty line. Occupation was unrelated to pressor responses to PE. These results suggest that neighborhood characteristics play an important role in cardiovascular functioning.

Although characteristics such as heart rate (HR) and blood pressure (BP) are commonly reported in studies of the relationship between fatigue and cardiac functioning, few reports examine how cardiac function parameters such as cardiac output (CO) and stroke volume (SV) relate to fatigue. This study examined the relationship between self-reported fatigue and hemodynamic functioning at rest and in response to a public speaking stressor in healthy individuals.A total of 142 individuals participated in this study. Subjects were placed in low-, moderate-, or high-fatigue groups based on their Profile of Moods State fatigue scale. Heart rate, SV, and CO were determined using impedance cardiography at rest and during a speaking stressor. Stroke volume and CO values were converted to stroke index (SI) and cardiac index (CI) by adjusting for body surface area. Data were analyzed with hierarchical regression analysis and a 3 (group) x 3 (stress period) mixed model analysis of variance.At rest, fatigue was not associated with BP or HR but was significantly associated with decreased CI (P.001; 95% confidence interval, -0.046 to -0.014) and stroke index (SI) (P = .002; 95% confidence interval -0.664 to -0.151), even after controlling for demographic variables and depressive symptoms. Heart rate and BP increased, as expected, from baseline to preparation to speaking stressor (F (1,124) = 118.6 and F (1,122) = 46.450, respectively) (P.001 for both). More interestingly, there were effects on SI and CI of fatigue (P.03 for both) and stress (P.03 for both); high-fatigue individuals had lower SI and CI levels than moderate- and low-fatigue individuals both at rest and in response to the stressor.This study demonstrates that fatigue complaints may have hemodynamic correlates even in ostensibly healthy individuals.

STUDY OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T

We hypothesized an association between heart rate variability (HRV) and plasminogen activator inhibitor (PAI)-1 that would be affected by body mass index (BMI). We determined PAI-1 antigen in plasma and the low-frequency power, high-frequency power and the low-frequency/high-frequency power ratio from surface electrocardiogram data using spectral analysis in a sample of 116 black and white men and women (mean +/- SE age, 36.8 +/- 0.7 years). Regression equations controlled for age, gender, ethnicity, smoking status, blood pressure, and BMI. We specifically tested whether BMI would moderate or mediate the relationship between HRV and PAI-1. There were bivariate correlations between PAI-1 and low-frequency power (r = -0.24, P = 0.010), high-frequency power (r = -0.41, P < 0.001), and the low-frequency/high-frequency power ratio (r = 0.19, P = 0.042). High-frequency power emerged as an independent predictor of PAI-1 levels (beta = -0.20, P = 0.040; DeltaR = 0.027) after controlling for covariates. The BMI significantly mediated the relationship between PAI-1 levels and low-frequency power (t = -2.77, P = 0.006) and high-frequency power (t = -2.99, P = 0.003). In conclusion, reduced parasympathetic activity (i.e. decreased high-frequency power) accounted for a small but significant amount of the variance in elevated PAI-1 levels. More apparent, higher BMI explained a significant proportion of the variance in the relationship between depressed sympathetic and parasympathetic activity and elevated plasma PAI-1 concentration.

Study Objectives: Daytime sleepiness is a common clinical presentation in both obstructive sleep apnea (OSA) and cardiovascular diseases. The purpose of this study was to assess the relationship between degree of subjective daytime sleepiness and cardiac performance in patients with obstructive sleep apnea. Design: Observational study Setting: General Clinical Research Center Patients: The study sample was comprised of 86 patients (68 men and 18 women) with an average age of 47 years. All were suspected of having obstructive sleep apnea and underwent confirmatory diagnostic polysomnography (respiratory disturbance index ≥ 15). Measurements and Results: Stroke volume and cardiac output were measured using impedance cardiography and corrected for body surface area to yield stroke index and cardiac index. Daytime sleepiness was quantified using the Epworth Sleepiness Scale. A higher Epworth Sleepiness Scale score, suggesting more daytime sleepiness, was significantly related to lower stroke index and cardiac index. In multiple regression analyses, the relationships of Epworth Sleepiness Scale score with both stroke index and cardiac index were significant (p < .05), even after controlling for age, sex, ethnicity, respiratory disturbance index, and mean sleep oxygen saturation. Conclusions: These results suggest that daytime sleepiness is independently associated with decreases in cardiac function as assessed by impedance cardiography in patients with obstructive sleep apnea.

Continuous positive airway pressure (CPAP) prediction formulas can potentially simplify the treatment of obstructive sleep apnea (OSA). However, they can be difficult to derive and validate. We tested a statistical method to derive and validate a CPAP prediction formula using the same sample population. Seventy-six OSA patients underwent polysomnography and CPAP titration. Anthropometric measures, sleep parameters, and the Epworth sleepiness scale (ESS) were evaluated as predictors. All subsets regression was used to determine the optimum number of variables in the model. The Bayes information criterion was used to find the best-fit model. The model was then evaluated by a tenfold cross-validation procedure. Subjects were obese (BMI 31.3 +/- 5.4) and had significant daytime somnolence (ESS 11.9 +/- 5). Mean respiratory disturbance index (RDI) was 53.5 +/- 31.3. The ESS was not predictive of titrated CPAP. The best-fit model included three variables (CPAP(pred) = 30.8 + RDI x 0.03 - nadir saturation x 0.05 - mean saturation x 0.2). This model explained 67% of the variance. Our data and the literature suggest that a combination of two to three factors is predictive of titrated CPAP: RDI, oxyhemoglobin saturation, and obesity. Except for RDI, the specific factors vary in each population. A CPAP prediction formula that explains a high proportion of the titrated CPAP variance can be easily derived from parameters measured during the diagnostic work-up of OSA patients using a unique statistical model that allows derivation and validation of the formula in the same test population.

OBJECTIVES: This study examined relationships among ethnicity, perceived discrimination, and vascular reactivity to phenylephrine (PE). METHODS: Seventy-six white patients and 46 black patients were studied at an inpatient clinical research center in response to a bolus intravenous injection of 100 microg PE. Self-report questionnaires assessed perceived discrimination. RESULTS: After controlling for body surface area, number of cigarettes smoked, and baseline blood pressure, black patients had greater vascular reactivity to PE than white patients (p = .01). There was also a significant relationship between perceived discrimination and diastolic blood pressure responsiveness to PE (p < .05). Path analyses revealed that perceived discrimination mediated the relationship between ethnicity and diastolic pressor responses. Individuals who perceived more discrimination had a larger increase in diastolic blood pressure in response to PE. CONCLUSION: These data suggest perceived discrimination is associated with increased blood pressure responsiveness to PE.

OBJECTIVE Low socioeconomic status (SES) is associated with low-grade inflammation. Vascular inflammation often accompanies high blood pressure (BP) and has clinical implications for future vascular diseases, including atherosclerosis. Elevated plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and endothelin-1 (ET-1) are reliable indicators of vascular inflammation. We examined the associations among BP, social status, and sICAM-1 and ET-1 levels in 121 European American and African American men and women. METHODS Social status of the subjects was determined by using the Hollingshead Two Factor Index of Social Position scale, and plasma sICAM-1 and ET-1 levels were assessed using immunoassays. RESULTS Correlation analyses revealed positive correlations among plasma sICAM-1 levels, BP, and social status. Levels of ET-1 were also significantly correlated with BP (p < .01) and social status (p < .001). When subjects were categorized into three social classes, sICAM-1 levels were significantly higher in the lowest social class as compared with the upper (p < .05) or middle (p < .01) class. The levels of ET-1 were higher in the low (p < .01) and middle (p < .05) social classes as compared with the upper class. Multiple hierarchic regression analyses revealed that even after controlling for demographic and health characteristics (gender, ethnicity, age, body mass index, and smoking) and systolic BP, social status accounted for additional variance of sICAM-1 or ET-1 levels. CONCLUSION These results suggest that low-social-status individuals may incur risk for future vascular diseases through vascular inflammation.

Fatigue is a common symptom, even among healthy individuals, but little is understood about it. We examined the associations among adiposity, depressive symptoms, cytokine levels, and multidimensional fatigue symptoms in otherwise healthy subjects. Furthermore, we examined whether obesity would account for a significant portion of fatigue and, if so, what kind of fatigue complaints appear to be related to obesity.Seventy healthy subjects (36 women and 34 men) with an average age of 36.0 years and at less than or equal to 170% of ideal body weight participated in the study. Participants had their height, weight, neck circumference, ratio of the waist to hip circumference, percentage of body fat, and plasma interleukin 6 and soluble intercellular adhesion molecule 1 concentrations measured. Their sleep was monitored with an overnight polysomnogram, and subjects completed the short form of the Multidimensional Fatigue Symptom Inventory, which measures 5 domains of fatigue, and the Center for Epidemiologic Studies-Depression Scale.Obesity, as measured by body mass index (calculated as weight in kilograms divided by the square of height in meters) and percentage of body fat, was associated with general fatigue. Depression scores were significantly related to all subscales of fatigue; the highest correlation was shown with emotional fatigue. The effect of obesity on physical fatigue was significant, even after controlling for depression. In general, interleukin 6 and soluble intercellular adhesion molecule-1 levels were unrelated to measures of fatigue.Obesity, cytokine concentrations, and depressive symptoms explained different dimensions of fatigue as measured by the short form of the Multidimensional Fatigue Symptom Inventory. Obesity accounted for a significant portion of physical fatigue after controlling for depressive symptoms and circulating levels of interleukin 6 and soluble intercellular adhesion molecule-1.