Disturbances in Melatonin, Cortisol and Core Body Temperature Rhythms after Major Surgery

Background It has been suggested that circadian rhythm disturbances are present after major surgery and that this may play a role in the development of postoperative sleep disturbances, fatigue, cognitive dysfunction and cardiovascular morbidity. The objective of this study was to examine the profile of melatonin, cortisol and core body temperature rhythms before and after major surgery. Methods Blood samples (melatonin and cortisol) and core body temperature readings were collected every hour in the 24-h period prior to surgery and the 48 h after surgery from 11 patients undergoing major abdominal surgery. All patients had private rooms. Light exposure was controlled and monitored. Phase markers [50% dim light melatonin onset (DLMO 50%) and offset (DLMOff 50%), cortisol and core body temperature acrophase] for the three circadian rhythm profiles were calculated before and after surgery. The correlation between the melatonin rhythm and time of surgery, duration of surgery and opioid use was examined. Results A median delay in the onset of melatonin was seen on the first postoperative day [median DLMO 50% 22:46 hours (range: 21:15–01:08 hours) on the preoperative day compared with 23:54 hours (range: 19:09–02:46 hours) on the first postoperative day; P ≤ 0.05] . A significant positive correlation existed between the duration of surgery and the time of melatonin onset (r = 0.67, P ≤ 0.05) . There was a significantly reduced basal secretion of melatonin immediately after surgery, with a subsequent significant increase in maximum melatonin values on the second postoperative night. A median delay of up to 4 h was seen in the timing of the peak of the temperature rhythm on the second postoperative day. Both cortisol secretion and core body temperature were increased after surgery and did not return to preoperative values in the 48 h of the postoperative study period. No significant correlation between opioid dose and the basal or maximum melatonin levels or the time of melatonin onset was found. Conclusion We found disturbances in three circadian markers after major surgery. The clinical consequences of postoperative circadian disturbances should be investigated further in the future.     

Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiod

Heart rate (HR) and heart rate variability (HRV) undergo marked fluctuations over the 24-h day. Although controversial, this 24-h rhythm is thought to be driven by the sleep-wake/rest-activity cycle as well as by endogenous circadian rhythmicity. We quantified the endogenous circadian rhythm of HR and HRV and investigated whether this rhythm can be shifted by repeated melatonin administration while exposed to an altered photoperiod. Eight healthy males (age 24.4 +/- 4.4 years) participated in a double-blind cross-over design study. In both conditions, volunteers were scheduled to 16 h-8 h rest : wake and dark : light cycles for nine consecutive days preceded and followed by 29-h constant routines (CR) for assessment of endogenous circadian rhythmicity. Melatonin (1.5 mg) or placebo was administered at the beginning of the extended sleep opportunities. For all polysomnographically verified wakefulness periods of the CR, we calculated the high- (HF) and low- (LF) frequency bands of the power spectrum of the R-R interval, the standard deviation of the normal-to-normal (NN) intervals (SDNN) and the square root of the mean-squared difference of successive NN intervals (rMSSD). HR and HRV variables revealed robust endogenous circadian rhythms with fitted maxima, respectively, in the afternoon (16:36 hours) and in the early morning (between 05:00 and 06:59 hours). Melatonin treatment phase-advanced HR, HF, SDNN and rMSSD, and these shifts were significantly greater than after placebo treatment. We conclude that endogenous circadian rhythmicity influences autonomic control of HR and that the timing of these endogenous rhythms can be altered by extended sleep/rest episodes and associated changes in photoperiod as well as by melatonin treatment.     

Outcomes of Stage I and II Breast Cancer with Nodal Micrometastases Treated with Mastectomy without Axillary Therapy

Breast Cancer Research and Treatment - Studies that report equivalent oncologic outcomes of sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for T1-2N1mi breast...     

Interrelationships of Violence and Psychiatric Symptoms in Women with Substance Use Disorders

Women's issues of violence, mental health problems, and substance abuse have been noted to cooccur, but few studies have examined the interrelationship among the three. A chart review of 198 women (primarily African American) at an inner city substance abuse treatment center was performed to collect data related to physical and sexual abuse experiences before and after age 13. There were significant associations among all forms of physical and sexual abuse before and after age 13 and most of the types of substances abused and almost all of the presenting mental health problems, but most of the independent relationships became nonsignificant in multivariate analyses. However, the experience of both physical and sexual assault increased the risk of suicide attempts by a factor of 6.04. Physical assault was a borderline (p = .07) predictor of depression, while sedative use was significantly predictive of depression, anxiety, and suicide attempts.     

Characterization of the biological roles of the estrogen receptors,ERalpha and ERbeta,in estrogen target tissues in vivo through the use of an ERalpha-selective ligand

Estrogens elicit many biomedically important responses in different target tissues, and the respective roles of the two estrogen receptors, ERalpha and ERbeta, in mediating these bioactivities is incompletely understood. In this study, we investigated the activity of an ERalpha-selective agonist ligand, propyl pyrazole triol (PPT), in several rat animal models to define the involvement of ERalpha in these biological responses. In a short-term (4 d) uterotrophic assay, PPT was found to be as efficacious as 17alpha-ethinyl-17beta-estradiol in stimulating uterine weight gain and up-regulating complement 3 gene expression. In a 6-wk chronic model, PPT completely prevented the ovariectomy-induced body weight increase and loss of bone mineral density. It also increased uterine weight and markedly reduced plasma cholesterol levels in these mature animals. PPT was also effective in the brain. It increased progesterone receptor mRNA in the arcuate and ventromedial nuclei of the hypothalamus and prevented experimentally induced hot flushes. Our findings indicate that several physiologically relevant estrogen-induced tissue responses can be effectively evoked via ERalpha alone. By providing an approach that is complementary to that of analyzing the phenotype and response of ER knockout animals, our findings also demonstrate that ER subtype-selective ligands can play a valuable role in enhancing our understanding of how estrogens work through the two ER subtypes.