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Biomedical subjects

A A Stone

Publications and source records attributed to A A Stone.

At least 19 recordsLinked to original sources

Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait components.

The cortisol rise after awakening (CAR) is a frequently applied measure of pituitary-adrenal activity. This measure seems to reflect the acrophase of the diurnal cycle and can easily be assessed in saliva samples, collected by the proband or patient under real life conditions. Since different state and trait factors affect the CAR, we here address the questions (a) to which extent state and trait factors affect the CAR, and (b) how often cortisol measures after awakening have to be taken to obtain reliable results. In this study, we assessed the CAR on 6 consecutive days. After applying structural equation models and correlation analyses, we conclude that (a) the CAR of a single day is determined to a great extent by situational factors and only for a small proportion by trait factors and (b) from two (AUC(t)) to six (AUC(i)) days are necessary to achieve reliable trait measures, since state factors bias data from a single day.

Adult↗

Allostatic load, perceived stress, and health: a prospective study in two age groups.

Overactivity of the hypothalamus-pituitary-adrenal axis (HPAA) has been observed in the presence of acute stress and, under chronic conditions, in disorders such as depression and anorexia nervosa as well as in cardiovascular and metabolic disorders. However, there may be other stress-related disorders (fatigue, pain, etc) that seem to be associated with mild hypocortisolism. This suggests that two major subtypes of the HPAA response to stress need to be discriminated. In this study, we investigated 76 subjects with and without hypocortisolism, respectively, over a 1-year period. Surprisingly, hypocortisolemic subjects had a lower allostatic load but they scored higher on measures of depression, perceived stress, and physical complaints. We propose a protective role of the hypocortisolemic stress response on cardiovascular and metabolic disorders, particularly in the elderly.

Adult↗

Emotional reactivity to daily life stress in psychosis.

BACKGROUND: The vulnerability-stress model of psychotic disorders describes, in essence, an interaction between personal vulnerability and environmental stressors. The present study investigated this interaction and studied emotional reactivity to daily life stress as a vulnerability marker for psychotic illness. METHODS: Patients with psychotic illness (n = 42), their first-degree relatives (n = 47), and control subjects (n = 49) were studied with the Experience Sampling Method (a structured diary technique assessing thoughts, current context, and mood in daily life) to assess (1) appraised subjective stress of daily events and smaller disturbances in daily life and (2) emotional reactivity conceptualized as changes in both negative affect and positive affect. RESULTS: Multilevel regression analyses showed that an increase in subjective stress was associated with an increase in negative affect and a decrease in positive affect in all groups. However, the groups differed quantitatively in their pattern of reactions to stress. Patients with psychotic illness reacted with more intense emotions to subjective appraisals of stress in daily life than control subjects. The decrease in positive affect in the relatives was similar to that of the patients, while the increase in negative affect in this group was intermediary to that of patients and control subjects. CONCLUSIONS: Higher levels of familial risk for psychosis were associated with higher levels of emotional reactivity to daily life stress in a dose-response fashion. Subtle alterations in the way persons interact with their environment may constitute part of the vulnerability for psychotic illness.

Adaptation, Psychological↗

Individual differences in the diurnal cycle of salivary free cortisol: a replication of flattened cycles for some individuals.

Free cortisol measured in saliva has been shown to have the same diurnal rhythm as serum cortisol, one that typically declines rapidly throughout the waking day. A recent study showed that over 15% of a sample of community individuals who were monitored over two days did not show the typical diurnal rhythm. The present study specifically tested the hypothesis that there is significant between-subject variation (individual differences) in diurnal rhythms using multi-level, random regression models. Analyses of participants from four studies were conducted; studies varied in terms of the number of saliva samples taken per day, the number of days studied, and participants' demographic and health status. Significant individual differences of diurnal cycle in each of the four samples were found. In at least 10% of each sample no significant diurnal cycles was detected; however, the overall mean level of cortisol of those with flat cycles differed among the samples. These results suggest that some people do not have the expected diurnal rhythm of cortisol secretion. It is not clear what the determinants of this finding are or if there are any health consequences of having a flat cycle.

Adolescent↗

Psychotherapy in the managed care health market.

The author considers the future of psychotherapy in the managed care health market. He focuses on two interrelated questions. How can the efficacy of psychotherapy be scientifically demonstrated? Can psychotherapy meet the standards of cost-effectiveness set by health plans? He notes that efficacy is not enough in the managed care market, in which health plans also focus on the rational allocation of resources and economies of scale. The author then turns to the question of whether the doctor-patient relationship, which was central to American medicine throughout much of the 20th century, can survive in the current healthcare climate. He reviews the literature on the efficacy of psychotherapy and discusses the criteria for empirically validated treatments proposed by the American Psychological Association. He concludes that there is considerable support for the premise that the personal qualities of the individual therapist that contribute to the formation of the therapeutic alliance are at least as important, if not more important, than the specific method of psychotherapy used. The author concludes that medicine and psychiatry may be neglecting an important and uniquely curative element-the doctor-patient relationship, the human encounter that is the foundation of the art and science of medicine.

Journal Article↗

Modulation of mitogen-activated protein kinases and phosphorylation of Bcl-2 by vinblastine represent persistent forms of normal fluctuations at G2-M1.

Microtubule inhibitors, widely used in cancer chemotherapy, induce G2-M arrest and apoptosis and have in common the ability to stimulate Raf-1/Bcl-2 phosphorylation and activate c-Jun NH2-terminal protein kinase (JNK). These signal transduction pathways are thought to be activated in response to microtubule damage to promote apoptosis. However, Bcl-2 phosphorylation has been reported to occur at G2-M in nonapoptotic cells, raising the possibility that this and perhaps other signaling pathways altered by microtubule inhibitors reflect perturbations of normal mitotic events. In this study, we sought to test this hypothesis. We show that Bcl-2 phosphorylation and JNK activation, as well as extracellular response kinase and p38 inactivation, occur not only in response to vinblastine but also as discrete transient events at G2-M phase in untreated synchronized KB-3 cells. Thus, modulation of these pathways is not a response to microtubule damage; rather they occur normally at G2-M, and it is the extent, duration, and/or irreversible nature of the signals that distinguish a preapoptotic cell from one destined to divide. These findings provide novel insight into the relationship between mitotic and apoptotic signaling and the mechanism of action of antimitotic drugs.

Activating Transcription Factor 2↗

Microtubule inhibitors elicit differential effects on MAP kinase (JNK, ERK, and p38) signaling pathways in human KB-3 carcinoma cells.

Microtubule inhibitors are widely used in cancer chemotherapy, but the signaling mechanisms that link microtubule disarray to destructive or protective cellular responses are poorly understood. Because members of the mitogen-activated protein kinase (MAPK) family have been implicated in regulation of cell survival and cell death, we examined the extent and kinetics of activation of JNK, ERK, and p38 MAPKs in response to treatment of KB-3 carcinoma cells with several microtubule inhibitors. All four agents tested (vinblastine, vincristine, Taxol, and colchicine) caused significant (6- to 13-fold) activation of JNK, concomitant inactivation of ERK, and a reduction in basal p38 MAPK activity. JNK activation and ERK inactivation occurred prior to caspase 3 activation. The microtubule inhibitors also induced phosphorylation of Raf-1 kinase. SEK-1, upstream of JNK, was also activated and phosphorylated in response to the microtubule inhibitors, and sustained phosphorylation of three endogenous JNK substrates (c-Jun, ATF-2, and JunD) was observed. By comparison, the antitumor agent doxorubicin induced activation of JNK and p38 but had no effect on ERK activity or Raf-1. These data demonstrate that microtubule inhibitors elicit distinct and specific effects on MAPK-mediated signaling pathways and suggest in particular that coordinate and reciprocal alterations in JNK and ERK activities are important facets of the cellular response to microtubule disruption.

Caspase 3↗

A naturalistic evaluation of cortisol secretion in persons with fibromyalgia and rheumatoid arthritis.

OBJECTIVE: To compare cortisol levels, diurnal cycles of cortisol, and reactivity of cortisol to psychological stress in fibromyalgia (FM) and rheumatoid arthritis (RA) patients in their natural environment, and to examine the effect on results of accounting for differences among the groups in psychological stress and other lifestyle and psychosocial variables. METHODS: Participants were 21 FM patients, 18 RA patients, and 22 healthy controls. Participants engaged in normal daily activities were signaled with a preprogrammed wristwatch alarm to complete a diary (assessing psychosocial- and lifestyle-related variables) or provide a saliva sample (for cortisol assessment). Participants were signaled to provide 6 diary reports and 6 saliva samples on each of two days. Reports of sleep quality and sleep duration were also made upon awakening. RESULTS: FM and RA patients had higher average cortisol levels than controls; however, there were no differences between the groups in diurnal cycles of cortisol or reactivity to psychological stress. While the groups differed on stress measures, surprisingly, the patient groups reported less stress. Furthermore, statistically accounting for psychosocial- and lifestyle-related differences between the groups did not change the cortisol findings. CONCLUSION: The results provide additional evidence of hypothalamic-pituitary-adrenal axis disturbance in FM and RA patients. While such elevations are consistent with other studies of chronically stressed groups, the elevations in cortisol in this study did not appear to be due to ongoing daily stress, and there was no evidence of disturbed cortisol reactivity to acute stressors.

Adult↗

Impact of gender and having children in the household on ambulatory blood pressure in work and nonwork settings: a partial replication and new findings.

Ambulatory blood pressure (ABP) has been shown to differ for men and women across work and nonwork settings. For men, ABP is higher at work than at home on workdays or on nonworkdays. For women, ABP levels in different settings depend on whether they have children in the household. Women without children at home exhibit the "male" pattern of higher ABP at work than at home. Women with children at home show either similar ABP levels in the two locations or higher ABP at home. These different patterns have been assumed to represent different stress levels in the two locations, but this assumption has rarely been tested. Also, few studies have examined ABP levels on a nonworkday in women or the effect of having children in the household for men. The present study monitored ABP in men and women during two workdays and one nonworkday. Comparisons were made between ABP levels in three settings (workday at work, workday at home, nonworkday) using mixed random effects regression models. Psychosocial variables (e.g. mood, stress) that might mediate the different ABP patterns were also assessed. ABP differences were analyzed by gender and whether children were living in the household using mixed random effects regression models. Results indicated that diastolic blood pressure was higher at work versus home for men with children and higher at work and on nonworkdays than at home for women without children. ABP did not differ across settings for women with children or men without children. These results were not mediated by mood or stress levels in the three settings.

Adult↗

Does the peak-end phenomenon observed in laboratory pain studies apply to real-world pain in rheumatoid arthritics?

Laboratory studies and investigations of patients undergoing painful procedures have compared recalled pain to an average of multiple momentary reports taken throughout the painful experience. This work has shown that recalled ratings of pain are more closely associated with a combination of peak pain and pain proximal to the recall ratings than an average of all momentary reports. However, these studies have examined recalled pain over relatively short periods, usually under 1 hour. In this study of 32 patients with rheumatoid arthritis, momentary pain ratings taken over a 7-day period were compared with pain recalled on the eighth day. Analyses confirmed that a combination of peak and recent pain was a better predictor of recalled patient pain than was a simple average of all momentary pain reports. These results extend our understanding of how individuals remember pain and suggest alternative methods for assessing recalled pain.

Journal Article↗

Structured writing about stressful events: exploring potential psychological mediators of positive health effects.

In a previous study, the authors found that structured writing about stressful events improved symptomatology in 112 patients with rheumatoid arthritis and asthma relative to patients who did not write (J. Smyth, A. Stone, A. Hurewitz, & A. Kaell, 1999). However, little is currently known about the pathways from the intervention to alterations in outcomes. In addition to measuring symptom outcomes after the intervention in the previous study, the authors monitored perceived stress, quality of sleep, affect, substance use, and medication use on a momentary basis for the 7 days prior to writing, during the 3 intervention days, and for the 14 days following the intervention (N = 105). These variables were tested in a secondary data analysis to determine whether they mediated the effects observed in the J. Smyth, A. Stone, et al. study. No evidence was found supporting mediation, and the mechanism underlying structured writing about stressful events remains unknown.

Adaptation, Psychological↗

Effects of writing about stressful experiences on symptom reduction in patients with asthma or rheumatoid arthritis: a randomized trial.

CONTEXT: Nonpharmacological treatments with little patient cost or risk are useful supplements to pharmacotherapy in the treatment of patients with chronic illness. Research has demonstrated that writing about emotionally traumatic experiences has a surprisingly beneficial effect on symptom reports, well-being, and health care use in healthy individuals. OBJECTIVE: To determine if writing about stressful life experiences affects disease status in patients with asthma or rheumatoid arthritis using standardized quantitative outcome measures. DESIGN: Randomized controlled trial conducted between October 1996 and December 1997. SETTING: Outpatient community residents drawn from private and institutional practice. PATIENTS: Volunteer sample of 112 patients with asthma (n = 61) or rheumatoid arthritis (n = 51) received the intervention; 107 completed the study, 58 in the asthma group and 49 in the rheumatoid arthritis group. INTERVENTION: Patients were assigned to write either about the most stressful event of their lives (n = 71; 39 asthma, 32 rheumatoid arthritis) or about emotionally neutral topics (n = 41; 22 asthma, 19 rheumatoid arthritis) (the control intervention). MAIN OUTCOME MEASURES: Asthma patients were evaluated with spirometry and rheumatoid arthritis patients were clinically examined by a rheumatologist. Assessments were conducted at baseline and at 2 weeks and 2 months and 4 months after writing and were done blind to experimental condition. RESULTS: Of evaluable patients 4 months after treatment, asthma patients in the experimental group showed improvements in lung function (the mean percentage of predicted forced expiratory volume in 1 second [FEV1] improved from 63.9% at baseline to 76.3% at the 4-month follow-up; P<.001), whereas control group patients showed no change. Rheumatoid arthritis patients in the experimental group showed improvements in overall disease activity (a mean reduction in disease severity from 1.65 to 1.19 [28%] on a scale of 0 [asymptomatic] to 4 [very severe] at the 4-month follow-up; P=.001), whereas control group patients did not change. Combining all completing patients, 33 (47.1%) of 70 experimental patients had clinically relevant improvement, whereas 9 (24.3%) of 37 control patients had improvement (P=.001). CONCLUSION: Patients with mild to moderately severe asthma or rheumatoid arthritis who wrote about stressful life experiences had clinically relevant changes in health status at 4 months compared with those in the control group. These gains were beyond those attributable to the standard medical care that all participants were receiving. It remains unknown whether these health improvements will persist beyond 4 months or whether this exercise will prove effective with other diseases.

Adaptation, Psychological↗

Managed care, liability, and ERISA.

Congress originally passed ERISA to secure the contractual benefits negotiated between employers and employees. In 1974, when the statute quickly moved through Congress, no one realized what its eventual significance for health care would be. Certainly no one expected that ERISA preemption would allow MCHPs to reduce professional standards of care while being protected from liability. The Department of Labor believes that it was never the intention of Congress to preempt ordinary damage claims for malpractice. There are now chinks in the legal armor of ERISA created by activists' courts as in the Dukes case. Even conservative Judges recognize the injustice of results, such as Corcoran. The American medical profession has traditionally complained about malpractice litigation and the wastefulness of defensive medicine. Perhaps ERISA will make the profession recognize that malpractice liability can serve a useful purpose.

Employee Retirement Income Security Act↗

Rheumatoid arthritis patients show weather sensitivity in daily life, but the relationship is not clinically significant.

While the majority of rheumatoid arthritis (RA) patients report that their pain is influenced by the weather, studies examining the impact of weather on RA pain have yielded equivocal results. It is not clear from the existing studies if the mixed results are due to limited statistical power (e.g. small sample sizes and restricted variability in weather indices) or the failure to consider individual differences. The current study addressed these weaknesses by having 75 RA patients (mean age = 52.7; 71% female) record their daily pain severity for 75 consecutive days. Objective weather indices including temperature, barometric pressure, relative humidity, and percentage of sunlight were obtained for the same dates from a local weather service. The results indicate that for the entire sample, pain levels were highest on cold, overcast days and following days with high barometric pressure. Pain levels also increased as a function of change in relative humidity from one day to the next. Individual difference analyses revealed significant variability between patients in their weather sensitivity patterns. In general, patients with higher levels of self-reported pain demonstrated more weather sensitivity. When considering the magnitude of these effects, however, weather variables accounted for only a small amount of change in pain scores. This pattern was true even for patients with the most pronounced pain-weather relationships. Thus, although weather sensitivity was found, the effect sizes were not clinically meaningful.

Adult↗

Daily psychosocial factors predict levels and diurnal cycles of asthma symptomatology and peak flow.

This study examines the relationship among psychosocial factors, asthma symptoms, and peak expiratory flow rate (PEFR) in the natural environment. Twenty adult asthmatics wore preprogrammed wristwatches that prompted them to assess PEFR, asthma symptoms, and psychosocial factors five times a day for 10 days. Psychosocial variables (activities, locations, social contacts, mood, and stressors) were strongly related to PEFR and asthma symptoms, suggesting that they may play a more important role in disease expression than has been previously thought. Diurnal cycles of asthma symptoms and PEFR were observed. However, statistically controlling for psychosocial factors eliminated diurnal cycles for PEFR or asthma symptoms, indicating that psychosocial factors are a major contributor to the observed diurnal cycle in PEFR and symptoms. These relationships underscore the need to include psychosocial factors in future asthma research.

Adaptation, Psychological↗