Biomedical subjects

Paul J Mills

Publications and source records attributed to Paul J Mills.

At least 19 recordsLinked to original sources

PubMed2006

The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review.

Increased cytokine and neopterin levels may be responsible for cancer-related fatigue, the most common complaint among cancer patients. We quantitatively reviewed empirical findings on this topic, focusing on studies not using immunotherapy. PubMed, PsychINFO and BIOSIS were searched for articles published until July 2006. Studies remained unweighted or were weighted according to study quality and sample size. The correlation coefficient r was used for statistical analyses. Heterogeneity among the studies was examined using the I(2) index. Eighteen studies (1037 participants) of moderately high methodological quality were located and statistically analyzed. Most studies measured more than one inflammatory marker, resulting in a total of 58 correlation estimates. In 31 of these, we had to input a null correlation because results had been simply reported as nonsignificant and no further statistical information was available. General analyses based on weighting according to sample size showed a significantly positive correlation between fatigue and circulating levels of inflammatory markers (r=0.11, p<0.0001). Analyses of individual inflammatory markers revealed significantly positive correlations between fatigue and IL-6 (r=0.12, p=0.004), fatigue and IL-1 ra (r=0.24, p=0.0005), and fatigue and neopterin (r=0.22, p=0.0001). Fatigue did not correlate significantly with IL-1 beta (r=0.05, p=0.42) or TNF-alpha (r=0.04, p=0.34). Given its preliminary nature due to the limited available data, this quantitative review showed a positive association between cancer-related fatigue and circulating levels of IL-6, IL-1 ra and neopterin. Future studies examining the relationship between cancer related fatigue and inflammation would benefit from multiple rather than single blood sampling and from repeated daily ratings of the multidimensional nature of fatigue.

Biomarkers↗

PubMed2006

Endocrinology: the active partner in PNI research.

For the past two decades, research appearing in the pages of Brain, Behavior, and Immunity (BBI), as well as other journals, has significantly deepened our understanding of the complexities of endocrine regulation of immunity in states of health and disease. This mini-review discusses contributions that endocrinology has made to the field of psycho-neuroimmunology (PNI), as well as discoveries that PNI researchers have made of the pervasive interactions between the endocrine and immune systems. We highlight the endocrine-immune interface, emphasizing similarities between the immune and endocrine systems as well as hormone/cytokine interactions. Differing endocrine-immune responses to acute and chronic psychosocial stress have been clarified during this time frame with the use of novel stress and endocrine sampling paradigms. Furthermore, investigations examining the role of cytokine involvement in acquired glucocorticoid resistance in illnesses like depression have expanded our understanding of the complexity of the endocrine-immune response to psychosocial stress. We have selected literature, with a focus on human studies, to illustrate these principals. We conclude with a discussion of the clinical relevance of endocrine-immune investigations and thoughts about the next decade of endocrine research in PNI.

Animals↗

PubMed2006

Stress-related reduction in personal mastery is associated with reduced immune cell beta2-adrenergic receptor sensitivity.

BACKGROUND: A growing body of literature suggests that caregiving burden is associated with impaired immune system functioning, which may contribute to elevated morbidity and mortality risk among dementia caregivers. However, potential mechanisms linking these relationships are not well understood. The purpose of this study was to investigate whether stress-related experience of depressive symptoms and reductions in personal mastery were related to alterations in ss2-adrenergic receptor sensitivity. METHODS: Spousal Alzheimer's caregivers (N = 106) completed measures assessing the extent to which they felt overloaded by their caregiving responsibilities, experienced depressive symptoms, and believed their life circumstances were under their control. We hypothesized that caregivers reporting elevated stress would report increased depressive symptoms and reduced mastery, which in turn would be associated with reduced ss2- adrenergic receptor sensitivity on peripheral blood mononuclear cells (PBMC), as assessed by in vitro isoproterenol stimulation. RESULTS: Regression analyses indicated that overload was negatively associated with mastery (beta = -0.36, p = 0.001) and receptor sensitivity (beta = -0.24, p = 0.030), whereas mastery was positively associated with receptor sensitivity (beta = 0.29, p = 0.005). Finally, the relationship between overload and receptor sensitivity diminished upon simultaneous entry of mastery. Sobel's test confirmed that mastery significantly mediated some of the relationship between overload and receptor sensitivity (z = -2.02, p = 0.044). CONCLUSIONS: These results suggest that a reduced sense of mastery may help explain the association between caregiving burden and reduced immune cell ss2-receptor sensitivity.

Adaptation, Psychological↗

PubMed2006

Depression in heart failure a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes.

This article describes a meta-analysis of published associations between depression and heart failure (HF) in regard to 3 questions: 1) What is the prevalence of depression among patients with HF? 2) What is the magnitude of the relationship between depression and clinical outcomes in the HF population? 3) What is the evidence for treatment effectiveness in reducing depression in HF patients? Key word searches of the Medline and PsycInfo databases, as well as reference searches in published HF and depression articles, identified 36 publications meeting our criteria. Clinically significant depression was present in 21.5% of HF patients, and varied by the use of questionnaires versus diagnostic interview (33.6% and 19.3%, respectively) and New York Heart Association-defined HF severity (11% in class I vs. 42% in class IV), among other factors. Combined results suggested higher rates of death and secondary events (risk ratio = 2.1, 95% confidence interval 1.7 to 2.6), trends toward increased health care use, and higher rates of hospitalization and emergency room visits among depressed patients. Treatment studies generally relied on small samples, but also suggested depression symptom reductions from a variety of interventions. In sum, clinically significant depression is present in at least 1 in 5 patients with HF; however, depression rates can be much higher among patients screened with questionnaires or with more advanced HF. The relationship between depression and poorer HF outcomes is consistent and strong across multiple end points. These findings reinforce the importance of psychosocial research in HF populations and identify a number of areas for future study.

Cardiac Output, Low↗

PubMed2006

Correlates of physical activity level in breast cancer survivors participating in the Women's Healthy Eating and Living (WHEL) Study.

BACKGROUND: Physical activity levels among breast cancer survivors are typically low, and knowledge of the correlates of increased physical activity among cancer survivors is limited. The purpose of this study was to examine factors that are associated with physical activity or inactivity among breast cancer survivors. METHODS: Data from 3088 women participating in the Women's Healthy Eating and Living (WHEL) Study, collected prior to randomization, were the focus of the current analyses. Self-reports of physical activity levels, quality of life, depression, and dietary intakes were collected. Pearson correlation analyses were employed to examine the associations among these variables, and multiple regression analyses were performed to examine the relationship between selected health behaviors and physical activity levels, after controlling for demographic, breast cancer-related, and psychosocial variables. RESULTS: Demographic and psychosocial variables were related to physical activity levels (P < 0.001 for all). Cancer treatment type and cancer stage were correlated with survivors' physical activity levels (P < 0.01), but the associations were no longer significant after controlling for demographic variables. Physical activity levels were strongly associated with other health behaviors, especially dietary intakes (P < 0.001), even after controlling for demographic, cancer-related, and psychosocial factors. CONCLUSION: Low physical activity levels in breast cancer survivors are associated with specific behavioral and other factors, which can be considered as indicators of women at higher risk. Findings of significant differences in physical activity levels based on demographic characteristics suggest the importance of promoting physical activity particularly among breast cancer survivors of ethnic minority or lower education levels.

Breast Neoplasms↗

PubMed2006

Physical fitness attenuates leukocyte-endothelial adhesion in response to acute exercise.

Studies suggest that physical fitness promotes cardiovascular health, including improved endothelial function and possibly reduced inflammatory responses to stressors. This study examined the effects of fitness on leukocyte-endothelial adhesion in response to an acute exercise challenge. Peripheral blood mononuclear cell (PBMC) adhesion to human umbilical venous endothelial cells (HUVEC) was examined in 18 more-fit and 19 less-fit individuals [mean age 39 yr (SD 11)] before and after a 20-min treadmill exercise at 65-70% peak oxygen consumption. PBMC were isolated from whole blood (Ficoll-Paque) at rest and immediately after exercise. HUVEC were incubated for 4 h in the presence of cytokines IL-1 and IL-8 to activate endothelial adhesion molecule expression. Fit subjects showed a significant reduction in PBMC-HUVEC adhesion after exercise (P < 0.01) compared with less-fit subjects, who showed no significant change. Regardless of fitness levels, both at rest and in response to exercise, soluble ICAM-1 in the incubation media attenuated PBMC-HUVEC adhesion by approximately 81% (P < 0.001). The findings indicate that immune cells that demarginate in response to exercise have reduced ability to adhere in individuals who are physically fit, an effect apparently independent of ICAM-1 binding. The findings provide evidence of how physical fitness might protect individuals from inflammatory responses to exercise.

Adaptation, Physiological↗

PubMed2006

Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure.

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 Ps <0.05). Although nocturnal supplemental oxygen therapy improved oxyhemoglobin saturation, it did not affect blood pressure. We conclude that CPAP therapy reduces both daytime and nighttime blood pressure in patients with OSA, perhaps through mechanisms other than improvement of nocturnal oxyhemoglobin saturation.

Adult↗

PubMed2006

Does obstructive sleep apnea increase hematocrit?

This study assessed the relationship between hematocrit levels and severity of obstructive sleep apnea (OSA) and examined how this relationship was affected by the degree of hypoxia as well as by possible confounding factors. Two-hundred sixty three subjects (189 men and 74 women) underwent nocturnal polysomnography with oximetry and had measurements of hematocrit, hemoglobin, white blood cell count, body mass index (BMI), blood pressure (BP), and 24-h urine norepinephrine (NE). Patients with severe OSA [respiratory disturbance index (RDI) >30] had significantly higher hematocrit values than patients with mild to moderate OSA or nonapneic controls (p < 0.01). However, only one patient had a hematocrit in the range of clinical polycythemia. Hematocrit levels were significantly correlated with BMI, BP, urinary NE, RDI, percent of time spent at oxygen saturation <90%, and with mean oxygen saturation. Multiple linear regression analysis revealed that mean oxygen saturation, RDI, and percent of time spent at oxygen saturation <90% were significant predictors of hematocrit level, even after controlling for gender, ethnicity, 24-h urine NE, BMI, and BP (p < 0.05). The severity of OSA is significantly associated with increased hematocrit, even after controlling for possible confounding variables. However, nocturnal hypoxemia in OSA does not usually lead to clinical polycythemia.

Adult↗

PubMed2006

Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and D-dimer.

BACKGROUND: Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the "frailty syndrome," defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. METHODS: Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 +/- 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. RESULTS: Caregivers had higher mean levels of IL-6 (1.38 +/- 1.42 vs 1.00 +/- 0.92 pg/mL, p =.032) and of D-dimer (723 +/- 530 vs 471 +/- 211 ng/mL, p <.001) than controls had. CRP levels were similar between groups (p =.44). The relationship between caregiver status and D-dimer was independent of covariates (p =.037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (beta =.20, p =.029) and of borderline significance for IL-6 (beta =.17, p =.090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (beta =.50, p <.001) and IL-6 (beta =.38, p =.001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. CONCLUSIONS: The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular diseases.

Age Factors↗

PubMed2006

Sleep disturbance, norepinephrine, and D-dimer are all related in elderly caregivers of people with Alzheimer disease.

STUDY OBJECTIVE: Caregiving for a relative with Alzheimer disease has been associated with sympathoadrenal medullary arousal and morbidity and mortality. In this study, we examined if sleep disturbance of elderly caregivers was associated with physiologic markers of cardiovascular risk, including plasma norepinephrine, epinephrine, and the hemostasis marker D-dimer. DESIGN: Cross-sectional. SETTING: Community-based sample of elderly caregivers of spouses with Alzheimer disease assessed within their homes. PARTICIPANTS: A sample of 40 elderly spousal caregivers of patients with Alzheimer disease. MEASUREMENTS AND RESULTS: Participants underwent in-home full-night polysomnography and had plasma assayed for norepinephrine and epinephrine. Using multiple regression analyses and controlling for a number of cardiovascular risk factors (e.g., age, sex, blood pressure, body mass index), increased wake after sleep onset was positively associated with norepinephrine levels (beta = .35; t = 2.45, df = 32, p = .020) and plasma D-dimer (beta = .31; t = 2.18, df = 29, p = .038). Further, plasma norepinephrine was significantly associated with D-dimer (beta = .34; t = 2.11, df = 29, p = .044). Additional analyses indicated that norepinephrine accounted for 28% of the relationship between wake after sleep onset and D-dimer. No association was observed between sleep variables and epinephrine. CONCLUSIONS: These findings provide preliminary evidence that sleep disturbance may contribute to morbidity in caregivers through sympathoadrenal medullary arousal and downstream physiologic effects such as altering the hemostasis environment.

Aged↗

PubMed2006

Avoidant coping partially mediates the relationship between patient problem behaviors and depressive symptoms in spousal Alzheimer caregivers.

OBJECTIVE: Caring for a loved one with Alzheimer disease is a highly stressful experience that is associated with significant depressive symptoms. Previous studies indicate a positive association between problem behaviors in patients with Alzheimer disease (e.g., repeating questions, restlessness, and agitation) and depressive symptoms in their caregivers. Moreover, the extant literature indicates a robust negative relationship between escape-avoidance coping (i.e., avoiding people, wishing the situation would go away) and psychiatric well-being. The purpose of this study was to test a mediational model of the associations between patient problem behaviors, escape-avoidance coping, and depressive symptoms in Alzheimer caregivers. METHODS: Ninety-five spousal caregivers (mean age: 72 years) completed measures assessing their loved ones' frequency of problem behaviors, escape-avoidance coping, and depressive symptoms. A mediational model was tested to determine if escape-avoidant coping partially mediated the relationship between patient problem behaviors and caregiver depressive symptoms. RESULTS: Patient problem behaviors were positively associated with escape-avoidance coping (beta = 0.38, p < 0.01) and depressive symptoms (beta = 0.26, p < 0.05). Escape-avoidance coping was positively associated with depressive symptoms (beta = 0.33, p < 0.01). In a final regression analysis, the impact of problem behaviors on depressive symptoms was less after controlling for escape-avoidance coping. Sobel's test confirmed that escape-avoidance coping significantly mediated the relationship between problem behaviors and depressive symptoms (z = 2.07, p < 0.05). CONCLUSION: Escape-avoidance coping partially mediates the association between patient problem behaviors and depressive symptoms among elderly caregivers of spouses with dementia. This finding provides a specific target for psychosocial interventions for caregivers.

Adaptation, Psychological↗

PubMed2006

Dementia severity of the care receiver predicts procoagulant response in Alzheimer caregivers.

BACKGROUND: The procoagulant factor D-dimer has been shown to be associated with thrombus formation and degradation as seen with conditions such as myocardial infarction and unstable angina. Research has demonstrated that spousal dementia caregivers have elevated levels of D-dimer relative to their non-caregiving peers. OBJECTIVE: The objective of this study was to determine the relationship of basal level and laboratory stressor-induced concentration of D-dimer to severity of dementia in spousal care recipients. METHODS: Seventy-one elderly caregivers were compared with a comparison group of 37 non-caregivers (average age: 71 years). Clinical Dementia Rating (CDR), a global measure of dementia, was used to assess severity of spousal dementia. Plasma D-dimer was measured at baseline and in response to an acute speech stressor. RESULTS: Regression analysis revealed a significant positive association between severity of spousal dementia and caregiver D-dimer, both at baseline and in response to acute stress, while controlling for age. The model examined an exponential relationship, with D-dimer increasing progressively across the span of dementia stages. DISCUSSION: Dementia severity of the care recipient was associated with increasing hypercoagulability among elderly caregivers. Effect size estimates suggest that such D-dimer increases may have clinical implications, particularly among late-stage caregivers.

Aged↗

PubMed2006

Personal mastery attenuates the effect of caregiving stress on psychiatric morbidity.

This study examined the protective effects of personal mastery on the relations between both objective and subjective stress and psychiatric morbidity in 79 spousal Alzheimer caregivers. Results indicated that with low mastery, the relations between patient problem behaviors and caregiver psychiatric symptoms was significant (t[71] = 2.03; p = 0.046). However, with high mastery, no significant association was found (t[71] = -0.76; p = 0.452). Similarly, the relations between role overload and psychiatric morbidity was significant when mastery was low (t[71] = 2.22; p = 0.029), but not high (t[71] = -1.49; p = 0.140). These results suggest that caregivers with a greater sense of personal mastery may be protected from the negative effects of caregiver stress.

Caregivers↗

PubMed2006

Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer's disease.

OBJECTIVES: To determine whether objective measures of sleep correlate with plasma levels of the proinflammatory cytokine interleukin (IL)-6 and the procoagulant marker fibrin D-dimer in caregivers of patients with dementia. DESIGN: Cross-sectional study. SETTING: Subjects' homes. PARTICIPANTS: Sixty-four community-dwelling spousal caregivers (69% women, mean age+/-standard deviation 72+/-9) and 36 sex-matched noncaregiving controls. MEASUREMENTS: All participants underwent in-home full-night polysomnography. Demographic and lifestyle factors, depression, diseases, and medication that could affect inflammation, coagulation, and sleep were controlled for in analyses regressing sleep variables and caregiver status and their interaction on plasma levels of IL-6 and D-dimer. RESULTS: Caregivers had higher levels of D-dimer (781+/-591 vs 463+/-214 ng/mL, P=.001) and IL-6 (1.42+/-1.52 vs 0.99+/-0.86 pg/mL, P<.06) and lower levels of total sleep time (369+/-70 vs 393+/-51 minutes, P=.049) and sleep efficiency (77+/-11 vs 82+/-9%, P=.04) than controls. After controlling for age and body mass index, longer wake time after sleep onset (change in coefficient of determination (DeltaR2)=0.039, P=.04) and the interaction between caregiver status and higher apnea-hypopnea index (DeltaR2=0.054, P=.01) were predictors of IL-6. Controlling for age, caregiver status independently predicted D-dimer levels (DeltaR2=0.047, P=.01). Controlling for age and caregiver status, lower sleep efficiency (DeltaR2=0.032, P=.03) and the interaction between caregiver status and more Stage 2 sleep (DeltaR2=0.037, P=.02) independently predicted plasma D-dimer levels. CONCLUSION: Poor sleep was associated with higher plasma IL-6 and D-dimer levels. These effects were most pronounced in caregivers of subjects with Alzheimer's disease. The findings suggest a mechanism that may explain how disturbed sleep might be associated downstream with cardiovascular risk, particularly in older people under chronic stress.

Aged↗

PubMed2006

Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by noradrenergic activation. Nasal continuous positive airway pressure (CPAP) is the treatment of choice and has been shown to effectively reduce elevated norepinephrine (NE) levels. This study examined whether the reduction in NE after CPAP is due to an increase in NE clearance and/or a decrease of NE release rate. Fifty CPAP-naive OSA patients with an apnea-hypopnea index >15 were studied. NE clearance and release rates, circulating NE levels, urinary NE excretion, and blood pressure and heart rate were determined before and after 14 days of CPAP, placebo CPAP (CPAP administered at ineffective pressure), or oxygen supplementation. CPAP led to a significant increase in NE clearance (P < or = 0.01), as well as decreases in plasma NE levels (P < or = 0.018) and daytime (P < 0.001) and nighttime (P < 0.05) NE excretion. NE release rate was unchanged with treatment. Systolic (P < or = 0.013) and diastolic (P < or = 0.026) blood pressure and heart rate (P < or = 0.014) were decreased in response to CPAP but not in response to oxygen or placebo CPAP treatment. Posttreatment systolic blood pressure was best predicted by pretreatment systolic blood pressure and posttreatment NE clearance and release rate (P < 0.01). The findings indicate that one of the mechanisms through which CPAP reduces NE levels is through an increase in the clearance of NE from the circulation.

Adult↗

PubMed2005

Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes.

Leukocytosis following exercise is a well-described phenomenon of stress/inflammatory activation in healthy humans. We hypothesized that, despite this increase in circulating inflammatory cells, exercise would paradoxically induce expression of both pro- and anti-inflammatory cytokines and growth factors within these cells. To test this hypothesis, 11 healthy adult men, 18-30 yr old, performed a 30-min bout of heavy cycling exercise; blood sampling was at baseline, end-exercise, and 60 min into recovery. The percentage of leukocytes positive for intracellular cytokines and growth factors and mean fluorescence intensity was obtained by flow cytometry. Proinflammatory cytokines (IL-1alpha, IL-2, IFN-gamma, and TNF-alpha), a pleiotropic cytokine (IL-6), and anti-inflammatory cytokines and growth factors [IL-4, IL-10, growth hormone (GH), and IGF-I] were examined. Median fluorescence intensity was not affected by exercise; however, we found a number of significant changes (P < 0.05 by mixed linear model and modified t-test) in the numbers of circulating cells positive for particular mediators. The pattern of expression reflected both pro- and anti-inflammatory functions. In T-helper lymphocytes, TNF-alpha, but also IL-6, and IL-4 were significantly increased. In monocytes, both IFN-gamma and IL-4 increased. B-lymphocytes positive for GH and IGF-I increased significantly. GH-positive granulocytes also significantly increased. Collectively, these observations indicate that exercise primes an array of pro- and anti-inflammatory and growth factor expression within circulating leukocytes, perhaps preparing the organism to effectively respond to a variety of stressors imposed by exercise.

Adolescent↗

PubMed2005

Interactive effects of common beta2-adrenoceptor haplotypes and age on susceptibility to hypertension and receptor function.

Few studies have examined to what extent genetic variants of the beta2-adrenoceptor (ADRB2) are involved in the development of hypertension with age, although beta2-adrenergic receptor responsiveness declines in older subjects. To investigate this, 10 common single-nucleotide polymorphisms (SNPs) in the promoter and coding regions of the ADRB2 gene were genotyped in an unrelated population consisting of 2 ethnic groups: European American (EA; n=610) and African American (AA; n=420). ADRB2 haplotypes were estimated by expectation maximization (EM) algorithm-based methods. In the general population for EAs and AAs, the variants of the ADRB2 gene, including the individual SNPs and their haplotypes, were not associated with hypertension. However, there was a significant interaction between age and one of the common haplotypes (haplotype 1) in EAs (P=0.01). Haplotype 1 was associated with protection against hypertension in young (< or =50 years of age) but not in old (>50 years of age) EAs (odds ratio, 0.5; 95% confidence interval, 0.27 to 0.91; P=0.02). This age-specific effect was further supported by the observations that young subjects carrying > or =1 copy of haplotype 1 had significantly lower diastolic blood pressure and nearly 2-fold higher ADRB2 binding density than the noncarriers (P<0.05). With aging, their ADRB2 numbers decreased to the level of the noncarriers, along with increased body mass index (7%; P<0.05) and decreased heart rate (7%; P<0.001). Our study suggests that age is an important modifier for the effects of ADRB2 polymorphisms on ADRB2 function and the development of hypertension.

Adult↗

PubMed2005

The relationship between fatigue and quality of life and inflammation during anthracycline-based chemotherapy in breast cancer.

Chemotherapy for breast cancer leads to increased fatigue, poor mood, and reduced quality of life. Few studies have examined possible changes in inflammation during chemotherapy as potential contributors to this phenomenon. This study examined the relationship among circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) and fatigue, depressed mood, and quality of life before and during anthracycline-based chemotherapy. Twenty-nine women diagnosed with stage I-IIIA breast cancer (mean age 49.5 years, S.D.+/-11) were studied prior to cycle 1 of chemotherapy and 2.5 months later at the start of cycle 4 of chemotherapy. Chemotherapy led to a significant increase in sICAM-1 (P<0.05) and VEGF (P<0.01) levels, as well as increased ratings of fatigue (P<0.01), depressed mood (P<0.03), and poorer quality of life (P<0.01). Multiple regression analyses revealed that elevated VEGF (P<0.01) and sICAM-1 (P<0.02) were related to the increased fatigue and/or poorer quality of life as a result of chemotherapy. Pre-chemotherapy levels of VEGF and pre-chemotherapy ratings of quality of life predicted quality of life in response to chemotherapy (P<0.001). The findings contribute to the literature by showing that both pre-chemotherapy and chemotherapy-induced changes in inflammation are related to changes in fatigue and quality of life in response to chemotherapy.

Adult↗