An investigation into socio-demographic-, health-, and cancer-related factors associated with cortisol and C-reactive protein levels in breast cancer survivors: a longitudinal study.

BACKGROUND: Breast cancer survivors (BCS) may exhibit dysregulated patterns of cortisol and C-reactive protein (CRP). The aims of this study were to describe BCS' cortisol and CRP levels over a 1-year period after treatment, and assess how levels relate to socio-demographic- (age, education level, marital status), health- (body mass index [BMI] category, menopausal status), and cancer-related factors (cancer stage, chemotherapy exposure, time since diagnosis). METHODS: Participants (N = 201) provided data at 3 months post-treatment (T1) and again 3, 6, 9, and 12 months later (T2-T5). At T1, participants completed self-report questionnaires and had their weight and height measured by a trained technician. At T1-T5, they provided five saliva samples at awakening, 30 min after awakening, 2:00 pm, 4:00 pm, and before bedtime on two nonconsecutive days to measure diurnal cortisol, and provided capillary whole blood to measure CRP. Data were analyzed using repeated-measure analyses of variance (ANOVAs) and mixed-design ANOVAs. RESULTS: Diurnal cortisol and CRP levels fluctuated over time. In univariate models, older age and post-menopausal status were associated with higher cortisol and CRP levels, higher cancer stage and chemotherapy were associated with lower cortisol levels, and higher BMI category was associated with higher CRP levels. In adjusted models, age was no longer associated with CRP levels and shorter time since diagnosis was significantly associated with higher CRP levels. CONCLUSIONS: Socio-demographic-, health-, and cancer-related factors may help identify BCS at risk of physiological dysregulation who need intervention. Identifying modifiable factors associated with cortisol and CRP will inform cancer care interventions.

Preconception Perceived Stress Is Associated with Reproductive Hormone Levels and Longer Time to Pregnancy.

BACKGROUND: Women who experience pregnancy loss are especially prone to high stress, though the effects of stress on reproductive outcomes in this vulnerable population are unknown. We assessed relationships between perceived stress and hormones, anovulation, and fecundability among women with prior loss. METHODS: One thousand two hundred fourteen women with 1-2 prior losses were followed for ≤6 cycles while attempting pregnancy and completed end-of-cycle stress assessments. For cycles 1 and 2, women also collected daily urine and completed daily perceived stress assessments. We assessed anovulation via. an algorithm based on human chorionic gonadotropin (hCG), pregnanediol-3-glucuronide (PdG), luteinizing hormone (LH), and fertility monitor readings. Pregnancy was determined via. hCG. Adjusted weighted linear mixed models estimated the effect of prospective phase-varying (menses, follicular, periovulatory, and luteal) perceived stress quartiles on estrone-1-glucuronide (E1G), PdG, and LH concentrations. Marginal structural models accounted for time-varying confounding by hormones and lifestyle factors affected by prior stress. Poisson and Cox regression estimated risk ratios and fecundability odds ratios of cycle-varying stress quartiles on anovulation and fecundability. Models were adjusted for age, race, body mass index (BMI), parity, and time-varying caffeine, alcohol, smoking, intercourse, and pelvic pain. RESULTS: Women in the highest versus lowest stress quartile had lower E1G and PdG concentrations, a marginally higher risk of anovulation [1.28; 95% confidence interval (CI) = 1.00, 1.63], and lower fecundability (0.71; 95% CI = 0.55, 0.90). CONCLUSION: Preconception perceived stress appears to adversely affect sex steroid synthesis and time to pregnancy. Mechanisms likely include the effects of stress on ovulatory function, but additional mechanisms, potentially during implantation, may also exist.

Quantitative profiling of cortisol metabolites in human urine by high-resolution accurate-mass MS.

Aim, materials & methods: Urinary cortisol profile has the potential as a diagnostic biomarker. We therefore developed a stable-isotope dilution ultraperformance chromatography multistage MS-based method to quantify cortisol and 16 metabolites in human urines. Results & conclusion: The LOD for cortisol and its metabolites ranges from 0.02 to 5.81 pg/µl urine. The inter- and intraday variations were 3.7-12.9% and 3.5-15.6%, respectively. Among the metabolites analyzed, significant person-to-person heterogeneity was observed, demonstrating the need for comprehensive metabolite profiling in diagnosis. Nevertheless, the glucuronides of dihydrocortisol, dihydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol and tetrahydrocortisone are the major ones. The sum of the glucuronidated and free forms constitute >93% of the metabolites analyzed, which is termed as total cortisol equivalent. Total cortisol equivalent may serve as a surrogate of cortisol secretion. Clinical trial registration number: NCT02500472.

Trajectory classes of cannabis use and heavy drinking among rural African American adolescents: multi-level predictors of class membership.

AIMS: To inform research on the etiology and prevention of substance use among rural African American youth by (a) identifying developmental trajectory classes of cannabis use and heavy drinking across adolescence and young adulthood and (b) examining associations between trajectory class membership and multi-level assessments of risk factors. DESIGN: A prospective study spanning 9 years with assessments of cannabis use and heavy drinking, the catecholamines epinephrine and norepinephrine, perceived stress and psychosocial risk factors. SETTING: Rural communities in the southeastern United States. PARTICIPANTS: African American youth (n = 518). MEASUREMENTS: Participants were assessed for cannabis use and heavy drinking at seven assessments beginning at 16 years of age and continuing to 25 years of age. At age 19, participants provided overnight urine voids that were assayed for catecholamines, a biological marker of life stress resulting from sympathetic nervous system activation. At ages 16 and 19, participants provided information on malleable psychosocial risk factors. FINDINGS: Latent class growth models revealed three distinct trajectory classes for cannabis use and for heavy drinking. Higher levels of circulating stress hormones and perceived stress were associated with classes reporting greater substance use over time (all Ps < 0.05). A composite of selected risk factors discriminated class membership (all Ps < 0.05). Trajectory classes characterized by rapid usage increases in early adulthood exhibited the greatest increase in deviant peer affiliations between ages 16 and 19 years. CONCLUSIONS: Rural African American youth's cannabis use and heavy drinking across adolescence and young adulthood demonstrate distinct developmental courses; a small number of risk factors and measures of biological and perceived stress differentiate class membership prognostically. Variability over time in these measures, specifically an increase in deviant peer affiliation, may help to account for steep increases in young adulthood.

Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage.

OBJECTIVE: Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. METHODS: This cross-sectional study included 6517 individuals aged 45 to 74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector. RESULTS: Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one-category increase of stress; ptrend = .025), even after adjusting for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG. CONCLUSIONS: In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.

The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

Additive contributions of childhood adversity and recent stressors to inflammation at midlife: Findings from the MIDUS study.

We examined the joint contributions of self-reported adverse childhood experiences (ACEs) and recent life events (RLEs) to inflammation at midlife, by testing 3 competing theoretical models: stress generation, stress accumulation, and early life stress sensitization. We aimed to identify potential mediators between adversity and inflammation. Participants were 1,180 middle-aged and older adults from the Midlife in the United States (MIDUS) Biomarker Project (M age = 57.3 years, SD = 11.5; 56% female). A composite measure of inflammation was derived from 5 biomarkers: serum levels of C-reactive protein, interleukin-6, fibrinogen, E-selectin, and ICAM-1. Participants provided self-report data regarding ACEs, RLEs, current lifestyle indices (cigarette smoking, alcohol consumption, physical exercise, waist circumference), current depressive symptoms, and demographic/biomedical characteristics. We also used indices of hypothalamic-pituitary-adrenocortical outflow (12-hr urinary cortisol) and sympathetic nervous system output (12-hr urinary norepinephrine and epinephrine). Analyses indicated that ACEs and RLEs were independently associated with higher levels of inflammation, controlling for each other's effects. Their interaction was not significant. The results were consistent with the hypothesis that associations between ACEs and inflammation were mediated through higher urinary norepinephrine output, greater waist circumference, smoking, and lower levels of exercise, whereas higher waist circumference and more smoking partially mediated the association between RLEs and inflammation. In support of the stress accumulation model, ACEs and RLEs had unique and additive contributions to inflammation at midlife, with no evidence of synergistic effects. Results also suggested that norepinephrine output and lifestyle indices may help explain how prior stressors foster inflammation at midlife.

A single pathophysiological pathway in Takotsubo cardiomyopathy: Catecholaminergic stress.

BACKGROUND: Takotsubo cardiomyopathy (TTC) continues to be under-diagnosed, due to its varying presentation, with potentially serious consequences if treatment is delayed. AIMS: To demonstrate the consistent involvement of catecholaminergic stress in TTC, regardless of the trigger. METHODS: Between 01 July 2009 and 31 August 2013, patients managed in our centre for thoracic pain syndrome, with or without troponin release, were followed up prospectively. TTC was diagnosed from the apical ballooning seen on left ventricular imaging (angiography or transthoracic echocardiography) in the absence of a significant coronary artery lesion. Triggers (emotional trauma, surgical stress and ß2-mimetic intoxication) were recorded; catecholamine-secreting tumours were screened for with a urinary methoxylate-derivative assay. RESULTS: TTC was diagnosed in 40 out of 2754 (1.5%) patients with thoracic pain syndrome, with or without troponin release. Triggers were emotional trauma (n=29, 72.5%), surgical stress (n=5, 12.5%), adrenergic intoxication (n=3, 7.5%) and catecholaminergic tumour (n=3, 7.5%). Mean left ventricular ejection fraction at admission was 38.0 ± 15.7%. Eight (20%) patients initially showed cardiogenic shock. In-hospital mortality was 7.5%, with no deaths from cardiogenic causes. Thirty-five (94.6%) of the survivors had recovered a normal left ventricular ejection fraction (> 55%) by discharge. CONCLUSION: Whatever the trigger, the common denominator in TTC is catecholaminergic stress. Classically suggested after emotional trauma, TTC may also be induced by surgical stress or endogenous or iatrogenic ß2-mimetic intoxication. The various contexts all have a similarly excellent cardiovascular prognosis if treated early.

Circulating and urinary adrenal corticosterone, progesterone, and estradiol in response to acute stress in female mice (Mus musculus).

In studies of stress, it can be difficult to obtain blood rapidly enough to avoid confounding steroid measures. Noninvasive urinary steroid measures may provide an alternative insofar as they reflect systemic steroids. In Experiment 1, we profiled urinary corticosterone, progesterone, and estradiol in ovariectomized female mice following 1 h on an elevated platform. This increased urinary corticosterone for 3 h and progesterone for 4 h. In Experiment 2, blood and urine samples were obtained at 0-6 h following stressor offset. Females showed increased serum corticosterone and progesterone immediately after stressor offset. Urinary corticosterone was increased at both 0 and 2 h post-stress, while an increase in progesterone 2-6 h after stressor offset was not significant. Estradiol was not influenced by this mild stressor. In Experiment 3, mice were exposed to a more severe 1 h stressor, a rat across a wire-mesh grid. In serum, both corticosterone and progesterone were elevated immediately after stressor offset and returned to baseline within 2 h. In urine, this severe stressor elevated corticosterone immediately and 2 h after stressor offset, and in progesterone 2 h after stressor offset. Estradiol in serum was not dynamic, but it was significantly elevated in urine 4 h after stressor offset. Urinary measures generally reflected systemic measures; however, with a different time course resulting in a longer return to baseline. We suggest that the relative value of serum or urinary steroid measures in mice depends upon the experimental design, and that estradiol may only respond when the stressor is severe.

A corticotropin-releasing factor receptor antagonist improves urodynamic dysfunction produced by social stress or partial bladder outlet obstruction in male rats.

Barrington's nucleus, in the pons, regulates micturition through spinal projections to preganglionic parasympathetic neurons. The stress neuropeptide CRF is prominent in these projections and has an inhibitory influence. Social stress in rats causes urinary retention and abnormal urodynamics resembling those produced by partial bladder outlet obstruction (pBOO), and this is associated with CRF upregulation in Barrington's nucleus. Here, we examined the role of CRF in social stress- and pBOO-induced urodynamic dysfunction by assessing the ability of a CRF1 receptor antagonist to alter these effects. Male rats exposed to repeated resident-intruder stress were administered vehicle or a CRF1 antagonist (NBI-30775) daily prior to the stress. Urodynamic function was recorded in the unanesthetized state 72 h after the final stress. NBI-30775 prevented the increased intermicturition interval, micturition volume, and bladder capacity produced by social stress, but not the increase in CRF expression in Barrington's nucleus neurons. The urinary dysfunction was also partly prevented by shRNA targeting of CRF in Barrington's nucleus, suggesting that stress-induced urinary dysfunction results, in part, from CRF upregulation in Barrington's nucleus and enhanced postsynaptic effects in the spinal cord. Finally, NBI-30775 improved urodynamic function of rats that had pBOO of 2-wk duration when administered daily during the second week but did not block the increase in CRF expression in Barrington's nucleus neurons. These findings implicate a role for Barrington's nucleus CRF in stress- and pBOO-induced urodynamic changes and suggest that CRF1 antagonists may be useful therapeutic agents for the treatment of urinary dysfunction.

Behavioral and perceived stressor effects on urinary catecholamine excretion in adult Samoans.

OBJECTIVES: The effects of perceptions and behaviors related to culturally patterned socioeconomic obligations on catecholamine excretion rates were studied in a cross-sectional sample of Samoan adults. METHODS: A total of 378 participants, ages 29-62 years, from 9 villages throughout Samoa, provided timed overnight urine specimens, and self-reported perceptions and behaviors associated with contributions to one's family, aiga, and chief, matai, and communal gift exchanges, fa'alavelave. Urinary norepinephrine and epinephrine excretion rates were measured by high performance liquid chromatography with electrochemical detection. Age (≤40 vs. >40 years) and gender-specific regression models were estimated to detect associations with catecholamine excretion. RESULTS: Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who view their contribution to their matai to be "just right," had significantly higher residence-adjusted norepinephrine excretion. Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who consider their contribution to their aiga not to be a burden, had higher epinephrine excretion. Older men who contribute more to their aiga and who perceive their contribution to their aiga to be "just right" had increased residence-adjusted epinephrine excretion. CONCLUSIONS: Individual-level perceptions and behaviors related to traditional socioeconomic obligations are a significant correlate of increased overnight catecholamine excretion rates. Higher excretion rates may be attributed to psychosocial stress arousal associated with a discordance between personal desires for upward social mobility, and family and community-based socioeconomic obligations. Changes in patterns of individual-level psychosocial stress arousal may contribute to cardiovascular disease risk in modernizing Samoans.

Employment and work schedule are related to telomere length in women.

OBJECTIVES: To examine the association of employment and work schedule with shorter DNA telomeres, a marker of cellular ageing and disease risk factor, and consider whether differences were related to health, behaviours and sociodemographic factors, or varied by stress levels or menopausal status. METHODS: This cross-sectional analysis of 608 women aged 35-74 in the Sister Study examined determinants of relative telomere length (rTL) measured by quantitative PCR in leucocyte DNA. Age-adjusted regression models estimated base pair (bp) rTL differences for current and lifetime schedule characteristics (ie, part-time, full-time or overtime hours; multiple jobs; irregular hours; shiftwork; work at night). Covariates included race, smoking, perceived stress, sleep, physical activity, health and menopausal status, education, marital status, live births, children under 18, measured body mass index and urinary stress hormones. RESULTS: Compared with non-employed women with moderate or substantial past work histories (n=190), those currently working full-time (n=247; median 40 h/week) had a shorter rTL, an age-adjusted difference of -329 bp (95% CI -110 to -548). Longer-duration full-time work was also associated with shorter rTL (age-adjusted difference of -472 bp, 95% CI -786 to -158 for 20+ vs 1-5 years). Findings were not explained by health and demographic covariates. However, rTL differences for working at least full-time were greater in women with higher stress and epinephrine levels. CONCLUSIONS: Current and long-term full-time work were associated with shorter rTL, with differences of similar magnitude to smoking and history of heart disease or diabetes. Longitudinal data with specific stress measures are needed to further evaluate the impact of work schedule on rTL.

Heart rate variability and urinary catecholamines from job stress in korean male manufacturing workers according to work seniority.

The aim of this study was to evaluate the relationships between job stress and indicators of autonomic nervous system activity in employees of the manufacturing industry. A total of 140 employees from a company that manufactures consumer goods (i.e., diapers and paper towels) were recruited for participation in this study. Job stress was assessed using Karasek's Job Content Questionnaire. Heart rate variability (HRV) was measured using a heart rate monitor, and urinary catecholamines were measured by an HPLC-ECD. Information on demographic characteristics, previous job history, smoking status and alcohol consumption was also collected. Job stress did not have a significant effect on HRV or catecholamines. However, low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. Low- and high-frequency HRV were higher in the high-strain group than in the low-strain group, but these differences were not statistically significant. The results of the present study indicate that low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. In addition, the results of this study show that HRV can be used as a potential physiologic indicator of job stress in employees with a short duration of employment.

Do blood pressure and heart rate responses to perceived stress vary according to endogenous estrogen level in women?

The results of experimental studies suggest that estrogen may blunt blood pressure responses to stress, but increase heart rate responses. We investigated whether within-person associations of perceived stress with blood pressure and heart rate during normal working life in 26 premenopausal and 7 postmenopausal women varied according to endogenous estrogen level. Each woman measured her own blood pressure and heart rate and completed a diary reporting perceived stress levels on six occasions on each of 2 working days. Premenopausal women were assessed once between days 4 and 6 of their menstrual cycle (low estrogen) and again between days 11 and 13 (high estrogen), and urine samples were taken to verify expected variation in estrogen level. Results showed that perceived stress was significantly positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate in the group as a whole. This association did not differ according to menopausal status. There was no difference in the association of perceived stress with SBP or DBP in premenopausal women according to day of assessment, but heart rate reactivity to perceived stress was significantly higher on the high-estrogen day. Our findings thus provide evidence that heart rate responses to perceived stress during everyday working life vary according to estrogen level in premenopausal women, but no evidence that blood pressure responses to stress vary according to endogenous estrogen level in women.

Evaluation of the effects of stress in cats with idiopathic cystitis.

OBJECTIVE: To determine the effects of stress in cats with feline idiopathic cystitis (FIC) by evaluating bladder permeability, sympathetic nervous system function, and urine cortisol:creatinine (C:Cr) ratios during periods of stress and after environmental enrichment. DESIGN: Prospective study. ANIMALS: 13 cats with FIC and 12 healthy cats. PROCEDURE: Cats subjected to an acute-onset moderate stressor for 8 days received IV injections of fluorescein. Serum fluorescein concentrations were determined and compared with those of controls to evaluate bladder permeability, and urine C:Cr ratios were compared to evaluate function of the hypothalamic-pituitary-adrenal (HPA) axis. Plasma catecholamine concentrations were analyzed in a subset of cats. After 8 days of moderate stress, cats were moved to an enriched environment, and tests were repeated after 21 days. RESULTS: Serum fluorescein concentrations were significantly higher in cats with FIC at all time points. In the cats in which plasma catecholamine concentrations were determined, concentrations of dihydroxyphenylalanine, norepinephrine, and dihyroxyphenylglycol were significantly higher in cats with FIC at all time points, whereas no differences in urine C:Cr ratio between groups were observed. CONCLUSION AND CLINICAL RELEVANCE: Cats with FIC appeared to have altered bladder permeability, most notably during the period of initial stress. The increase in plasma dihydroxyphenylalanine concentration suggests that there may be stress-induced increase in the activity of tyrosine hydroxylase, which catalyzes the rate-limiting step in catecholamine synthesis. In contrast, no effects of stress on C:Cr ratios were observed, which suggests there was dissociation between the sympathetic nervous system and HPA-axis responses to stress.

Urinary catecholamine levels in daily life are elevated in women at familial risk of breast cancer.

Recent experimental research has shown that women facing the chronic stress of being at familial risk of breast cancer have greater neuroendocrine reactivity responses to stressful laboratory tasks. Whether this enhanced stress response also occurs outside the laboratory under daily life conditions is unknown. In the present study, urinary epinephrine and norepinephrine excretion rates at work (e.g. 11:00 AM-3:00 PM), home (e.g. 6:00 PM-10:00 PM) and during sleep (e.g. 10:00 PM-6:00 AM) were compared between 73 employed women with family histories of breast cancer in first degree relatives (FH+; age=36.8+/-8.7) and 81 without such family histories (FH-; age=38.1+/-9.4). Differences in sympathetic adrenal medullary responses to an ordinary life stressor (work) were assessed in naturalistic settings. Repeated measures MANCOVA with family history group as a fixed factor, body mass index as a covariate and daily microenvironment (work, home and sleep) as a repeating factor were conducted to evaluate whether catecholamine excretion rates differed between FH+ and FH- groups. The results revealed that women with family histories of breast cancer had a higher rate of epinephrine excretion while at work (p<0.005). In addition, women in the FH+ group were also more reactive to the stress of work, showing a greater percentage of increase in both epinephrine and norepinephrine from sleep to work (p<0.05). The results also indicated that the chronic stress effects associated with a family history of breast cancer were moderated by BMI, such that their impact was more pronounced and apparent when women were not obese. These findings support the idea that the heightened neuroendocrine reactivity to experimental stressors in women at familial risk of breast cancer also occurs when women encounter stressors in ordinary life (work stress). Additional research to explore the health consequences of increased reactivity in women at familial risk of breast cancer, and perhaps in individuals at familial risk of other life-threatening disease, would appear warranted.

Benzodiazepine premedication may attenuate the stress response in daycase anesthesia: a pilot study.

PURPOSE: Patients undergoing daycase surgery suffer from varying degrees of fear and anxiety. There is conflicting evidence in the literature regarding the benefit of benzodiazepine premedication in daycase surgery. We carried out a prospective, double-blind, randomized pilot study investigating the effect of benzodiazepine premedication on the stress response in patients undergoing daycase anesthesia and surgery. METHODS: Group I (n = 16) received diazepam 0.1 mg*kg(-1) orally 60 min preoperatively; Group II (n = 15) received diazepam 0.1 mg*kg(-1) orally 90 min preoperatively; Group III (n = 30) received a placebo. The stress response was measured by analyzing urinary catecholamine and cortisol levels and by scoring anxiety levels using state-trait anxiety inventory (STAI) scores and visual analogue scores (VAS). RESULTS: Anxiety scores (VAS and STAI scores) were not different between groups. We found a statistically significant reduction in urinary cortisol and noradrenaline levels in the groups receiving diazepam vs placebo. DISCUSSION: The reduction in stress hormones following diazepam premedication, in patients undergoing daycase surgery may support the role for benzodiazepine premedication in this setting. However, further studies are warranted to determine the clinical significance of these findings.

Intraoperative stress experienced by surgeons and assistants.

BACKGROUND AND OBJECTIVE: To determine the intraoperative stress on surgeons and assistants during cataract surgery, 12 surgeons and 3 assisting nurses were assessed based on their level of professional experience. METHODS: Surgeons were classified as inexperienced, intermediate, or experienced. Nurse assistants were classified as inexperienced or experienced. The intraoperative heart rates and urine adrenaline levels of each participant were measured. RESULTS: Inexperienced surgeons and nurse assistants had the highest heart rates at the beginning of surgery, and the rates tended to decrease toward the end of surgery. All values were higher than the other two groups throughout surgery. In surgeons with intermediate experience, the heart rates were not as high as in the inexperienced personnel; however, the heart rates were high throughout the surgery. The heart rate in one intermediate surgeon was markedly increased when a surgery was simultaneously broadcast on closed-circuit television. In experienced surgeons and a nurse assistant, the measurements increased slightly. CONCLUSIONS: The variations in heart rates and urine adrenaline levels showed characteristic patterns based on the experience of the surgical personnel.

Altered cortisol response in sober alcoholics: an examination of contributing factors.

We have previously reported an attenuated plasma cortisol stress response in alcoholics abstinent from alcohol up to 4 weeks. The present study replicates and extends these findings by examining urinary cortisol levels in detoxified alcoholics (n = 40) and controls (n = 14) at rest and following mental arithmetic and isometric handgrip stress. Although the groups had similar baseline cortisol levels, the alcoholics showed an attenuated cortisol response to the combined stressors. This cortisol response reduction was unrelated to potential confounds such as smoking, liver function, age, depression, or anxiety. A multivariate model showed a trend for an association between severity of withdrawal and alcoholics' poststress cortisol levels. Although these results indicate decreased adrenocortical response to biobehavioral stress in alcoholics abstinent up to four weeks, higher stress cortisol values were seen in the patients with the most severe withdrawal symptoms.

Meditation, melatonin and breast/prostate cancer: hypothesis and preliminary data.

The objective of this study was to test the hypothesis that the regular practice of mindfulness meditation is associated with increased physiological levels of melatonin. Melatonin may be related to a variety of biologic functions important in maintaining health and preventing disease, including breast and prostate cancer. Previous studies have shown melatonin production is photosensitive and we suggest here that it also may be psychosensitive. A cross-sectional study of 12-hour (20:00-08:00) urinary 6-sulphatoxymelatonin was conducted from which we analyzed data from 8 women who regularly meditate (RM) and 8 women who do not meditate (NM). All samples were collected in the homes of study participants. Volunteers were recruited to provide 12-hour overnight samples of urine. All subjects collected the samples on one night during the same 1-week period. There was no explicit intervention. However, all RM were either graduates of, or teachers in, the University of Massachusetts Stress Reduction and Relaxation Program. The main outcome measure was the total excretion of urinary 6-sulphatoxymelatonin. Multiple linear regression (Proc GLM in SAS) was performed to test the effect of meditation (RM vs NM) on 6-sulphatoxymelatonin. The results of the study were that after controlling for the non-significant effect of menstrual period interval, we found an effect of meditation group (RM vs NM: b = 1.983; F = 6.78; p = 0.02) and age (for each integer year: b = 0.169; F = 8.41; p = 0.01). The conclusion is that study results are consistent with our hypothesis and indicate that melatonin might be a useful parameter in testing similar psycho-social interventions.(ABSTRACT TRUNCATED AT 250 WORDS)