Association of Worse Prognosis With an Aberrant Diurnal Cortisol Rhythm in Patients With Advanced Lung Cancer

A flatter diurnal rhythm of cortisol has been reported to be associated with early mortality in patients with metastatic breast cancer. The clinical stage of disease at the time of diagnosis and the patient's performance status (PS) are known to be important prognostic factors for lung cancer (LC) survival. The authors examined the relationship between diurnal cortisol rhythms and these prognostic factors in patients with advanced LC. Cortisol concentrations were measured in saliva samples collected from 52 patients (37 males/15 females) with advanced LC and from 56 healthy subjects (32 males/24 females) to characterize the diurnal cortisol rhythm, specifically the cortisol awakening response (CAR) and diurnal cortisol decline (DCD). Variations of CAR and DCD in the patients were analyzed according to their clinical disease stage and PS score, and the differences in CAR and DCD between patients and healthy controls were compared. The patient group showed significantly reduced diurnal cortisol secretory activity and rhythmicity, compared with healthy controls. When the patients were subgrouped according to their clinical disease stage, patients with stage 4 disease showed significantly reduced CAR and flatter DCD compared with the healthy controls. However, the CAR and DCD in patients with stage 3a and 3b disease were comparable to those of healthy controls. Neither the CAR nor the DCD showed stepwise changes as the disease stage worsened. When patients were subgrouped according to their Eastern Cooperative Oncology Group (ECOG) PS score, there was stepwise reduction in the CAR and flattening of the DCD as the PS score increased. Both an abolished CAR and a flattened DCD were common in patients with ECOG PS scores of 3 and 4. These results indicate that alteration of the diurnal cortisol rhythm in patients with advanced LC is more closely associated with their PS score than with their clinical disease stage. Gradual alteration of the CAR and DCD, indicative of loss of 24-h cortisol rhythm, in concert with increase in PS score implies that endogenous circadian rhythms may also be disintegrating as the PS score worsens in these patients. (Author correspondence: ryunsup@yahoo.co.kr)     

Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study

Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic-pituitary-adrenal (HPA) axis early in life. In 366 infants aged 12-20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires.We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis.     

Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression

To investigate whether depression is accompanied by changes in diurnal rhythms of free estradiol and cortisol in different phases of the menstrual cycle, we measured these two hormone levels in saliva samples collected every 2 h for 24 h from 15 healthy normally cycling women and 12 age-matched normally cycling women suffering from major depression taking antidepressants. The assessments were repeated four times over one menstrual cycle: during menstruation and in the late follicular/peri-ovulating, early to mid-luteal and late luteal phases, respectively. Quantification with a nonlinear periodic regression model revealed distinct diurnal rhythms in free estradiol and free cortisol in all subjects. For the diurnal cortisol rhythm, significant differences were found in the peak-width and ultradian amplitude among different menstrual phases, both in controls and depressed patients, while no significant differences were found between the two groups. The diurnal estradiol rhythm, on the other hand, was quite consistent among different menstrual phases within both groups, while the depressed patients had overall larger amplitudes than controls, which is negatively correlated with disease duration. Significant positive correlations between the two hormone rhythms were found for 24-h mean level (mesor), peak, and trough in late luteal phase, and for ultradian harmonics in early to mid-luteal phase in controls, but only for ultradian harmonics in late follicular/peri-ovulating phase and for acrophase in the menstruation phase in depressed patients. A sub-analysis was also performed in patients who received Fluoxetine (n = 7). The findings implicate a close correlation between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis, both of which may be involved in depression.     

Is There an Association between Work Stress and Diurnal Cortisol Patterns? Findings from the Whitehall II Study

Objective

The evidence on whether there is work stress related dysregulation of the hypothalamic-pituitary-adrenal axis is equivocal. This study assessed the relation between work stress and diurnal cortisol rhythm in a large-scale occupational cohort, the Whitehall II study.

Methods

Work stress was assessed in two ways, using the job-demand-control (JDC) and the effort-reward-imbalance (ERI) models. Salivary cortisol samples were collected six times over a normal day in 2002–2004. The cortisol awakening response (CAR) and diurnal cortisol decline (slope) were calculated.

Results

In this large occupational cohort (N = 2,126, mean age 57.1), modest differences in cortisol patterns were found for ERI models only, showing lower reward (β = −0.001, P-value = 0.04) and higher ERI (β = 0.002, P-value = 0.05) were related to a flatter slope in cortisol across the day. Meanwhile, moderate gender interactions were observed regarding CAR and JDC model.

Conclusions

We conclude that the associations of work stress with cortisol are modest, with associations apparent for ERI model rather than JDC model.     

Factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer patients

ObjectivesThis study aimed to explore factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer (aNSCLC) patients treated with immune checkpoint inhibitors (ICIs).MethodsA total of 101 patients with aNSCLC receiving ICIs were included. The association between clinical factors and multiple endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) were investigated by multivariate analyses.ResultsMultivariate logistic analyses revealed that clinical stage, lactate dehydrogena (LDH), and any grade immune-related adverse events (irAEs) were independent predictors of ORR, while LDH and ICIs treatment type were independent predictors of DCR. In Multivariate Cox analysis, Eastern Cooperative Oncology Group performance status (ECOG PS), LDH, albumin (Alb), platelet to lymphocyte ratio (PLR), and any grade irAEs were independent factors for OS. Similarly, clinical stage, LDH, Alb, and any grade irAEs were independent factors for PFS. Pre-treatment prognostic score was established based on clinical stage, ECOG PS, LDH, Alb and PLR to classify patients into three groups: the good group (0–1 score), the intermediate group (2 scores) and the poor group (3-4 scores). The immunotherapy response was significantly different in various prognostic groups. Subset analyses showed pre-treatment prognostic score ≥ 3 tended to have a strong negative impact on survival among patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 50%.ConclusionsPre-treatment prognostic score based on clinical stage, ECOG PS, LDH, Alb and PLR may help to identify aNSCLC patients who may benefit from ICIs.     

Beyond physiological hypoarousal: The role of life stress and callous-unemotional traits in incarcerated adolescent males

The development of antisocial behavior in youth has been examined with neurobiological theories that suggest that adolescents who are less responsive to their environments are less likely to develop empathy in the absence of extant physiological arousal. However, little attention is paid to these individuals' social context. Individuals with adverse early experiences can also exhibit attenuated physiological arousal. The current investigation examines whether psychopathic symptoms or life stress exposure is associated with cortisol and its diurnal rhythm within 50 incarcerated adolescent boys (14–18 years old). Ten saliva cortisol samples were collected 1–2 weeks after admission to a maximum-security juvenile facility. Hierarchical Linear Modeling distinguished waking cortisol levels, the awakening response (CAR) and the diurnal rhythm. Multiple interviews and self-report measures of CU traits and stressor exposure were collected. Boys with higher levels of CU traits or greater life stress exposure had flat diurnal rhythms and a steeper awakening response in analyses with lifetime stress exposure specifically. Nonetheless, boys who were elevated on both CU traits and prior stress exposure had steeper diurnal rhythms. These results extend neurobiological theories of cortisol and illustrate that boys with the combination of severe stress with CU traits have a unique physiological profile.     

Self-reported symptoms of depressed mood, trait anxiety and aggressive behavior in post-pubertal adolescents: Associations with diurnal cortisol profiles

The association between self-reported symptoms and diurnal cortisol profiles was studied in post-puberty adolescents (29 boys and 29 girls, M_age = 15.06 years). The adolescents completed the Children's Depression Inventory, State Trait Anxiety Inventory, and an Aggressive behavior scale. The diurnal cortisol profile was derived from three saliva samples, collected at awakening, noon and evening on a week-end day. Univariate repeated measurement regressions revealed that depressed mood and trait anxiety were strongly and aggressive behavior was weakly related to the diurnal cortisol profile: greater emotional distress was associated with flatter diurnal cortisol profiles. Multivariate analysis, however, revealed that only trait anxiety made an independent contribution. Further analyses suggested that trait anxiety was related to elevated evening cortisol rather than to decreased awakening cortisol and that from a trait anxiety score of 38 onwards, high anxious adolescents show clearly higher evening cortisol than low anxious adolescents. These data suggest that anxiety disorder co-morbidity might explain some of the differences in HPA-axis function among depressed patients.     

High correlation between salivary cortisol awakening response and the psychometric profiles of healthy children

Background

Cortisol awakening response (CAR) as an indicator of psychological stress and related physical and psychiatric diseases has attracted growing attention from researchers. Although CAR changes have been investigated extensively in children with behavioral and psychiatric disorders, the association between CAR and conventional psychometric scales for healthy children has not been reported. The aim of this study was to investigate the association between salivary CAR and subscales of Profiles of Mood States (POMS), a self-assessment questionnaire widely used to evaluate the temporal emotional states of healthy children.

Findings

This study included 18 healthy girls aged 13–16 years. Saliva was collected immediately on awakening, 30 min and 60 min after waking, and then at 2-hour intervals from 9 am to 5 pm. The current mood state, including depression, anxiety, fatigue, and other psychometric profiles were assessed using POMS. The magnitude of salivary CAR and the area under the concentration-time curve (AUC) for diurnal salivary cortisol were compared with the profiles. There were significant positive correlations between the magnitude of CAR and the POMS subscales for "Depression-Dejection", "Tension-Anxiety", "Fatigue", and "Confusion". No correlation was found between the AUC salivary cortisol level and the psychometric profiles.

Conclusions

Salivary CAR was associated with various mood states of healthy female children but diurnal salivary cortisol AUC was not. Salivary CAR may be a biomarker of the physical and mental condition of healthy female children.

     

Racial and ethnic differences in diurnal cortisol rhythms in preadolescents: the role of parental psychosocial risk and monitoring

Racial/ethnic minorities experience persistent health disparities due in part to their exposure to chronic SES and psychosocial risk. The hypothalamic-pituitary-adrenal axis and its hormonal end product, cortisol, are believed to mediate the associations between chronic stress and poor health. In this study, racial/ethnic differences in diurnal salivary cortisol rhythms in 179 preadolescent youths and the contributing roles of SES risk, psychosocial risk, perceived discrimination, harsh parenting, and parental monitoring were examined. The analyses revealed racial/ethnic differences in diurnal cortisol rhythms, with African Americans having significantly flatter morning-to-evening cortisol slopes than Caucasians and with Latinos having significantly lower evening cortisol levels than Caucasians. Greater psychosocial risk and less parental monitoring were associated with flatter cortisol slopes. Racial/ethnic differences on the cortisol measures persisted when controlling for SES, psychosocial risk, and parenting quality. The need to assess chronic risk across the lifespan and disentangle possible genetic from environmental contributors is discussed.     

Is HPA axis reactivity in childhood gender-specific? A systematic review

Background

In adults, hypothalamus–pituitary–adrenal (HPA) axis activity shows sexual dimorphism, and this is thought to be a mechanism underlying sex-specific disease incidence. Evidence is scarce on whether these sex differences are also present in childhood. In a meta-analysis, we recently found that basal (non-stimulated) cortisol in saliva and free cortisol in 24-h urine follow sex-specific patterns. We explored whether these findings could be extended with sex differences in HPA axis reactivity.

Methods

From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed HPA axis reactivity in healthy girls and boys aged ≤18 years. Articles were systematically assessed and reported in the categories: (1) diurnal rhythm, (2) cortisol awakening response (CAR), (3) protocolled social stress tests similar or equal to the Trier Social Stress Test for children (TSST-C), (4) pharmacological (ACTH and CRH) stress tests, and (5) miscellaneous stress tests.

Results

Two independent assessors selected 109 out of 6158 records for full-text screening, of which 81 studies (with a total of 14,591 subjects) were included. Studies showed that girls had a tendency towards a more variable diurnal rhythm (12 out of 29 studies), a higher CAR (8 out of 18 studies), and a stronger cortisol response to social stress tests (9 out of 21 studies). We found no evidence for sex differences in cortisol response after a pharmacological challenge or to miscellaneous stress tests.

Discussion

Sex differences in HPA axis reactivity appear to be present in childhood, although evidence is not unequivocal. For a better evaluation of sex differences in HPA axis reactivity, standardization of protocols and reports of stress tests is warranted.

     

General and unspecific damping by malignancy of the circadian amplitude of circulating human melatonin?

The circadian rhythm of serum melatonin of 39 cancer patients is compared with that of 28 healthy subjects matched by gender and age. Each subject provided 6 blood samples at 4-hour intervals for determination of melatonin by RIA. After log10-transformation, data series were analyzed by single and population-mean cosinor and compared between the two groups and among patients subgrouped by cancer site, stage and treatment. A circadian rhythm (P<0.001) is demonstrated for both groups, with a contributing 12-hour harmonic (P<0.001). In the absence of a difference in MESOR, the circadian amplitude of the cancer patients is smaller than that of the healthy subjects (P=0.003). Numerically, nocturnal (00:00 and 04:00) melatonin concentrations are lower and daytime (08:00-20:00) melatonin concentrations are higher in the cancer patients than in the healthy subjects (P=0.032 at 12:00 and P=0.058 at 16:00). In the age ranges examined, no differences are found with age in either group or by gender in health. No differences are found among cancer patients subgrouped either by site, stage (localized vs. metastasized) or treatment. If these results are validated, other Janus-like (two-faced: stimulation or inhibition, depending on chronome stage) effects of malignancy should be taken into consideration for screening and for timing treatment.     

High self-perceived stress and many stressors, but normal diurnal cortisol rhythm, in adults with ADHD (attention-deficit/hyperactivity disorder)

Attention-deficit/hyperactivity disorder (ADHD) in adults is associated with significant impairment in many life activities and may thus increase the risk of chronic stress in everyday life. We compared adults with a DSM-IV ADHD diagnosis (n = 28) with healthy controls (n = 28) regarding subjective stress and amounts of stressors in everyday life, diurnal salivary cortisol in the everyday environment and salivary cortisol before and after cognitive stress in a laboratory setting. The association between cortisol concentrations and impulsivity was also investigated. Consistent with assumptions, individuals with ADHD reported significantly more self-perceived stress than controls, and subjective stress correlated with the amount of stressors in everyday life. The two groups were comparable with respect to overall diurnal cortisol levels and rhythm, as well as in pre- and post-stress cortisol concentrations. Post-stress cortisol (but not baseline cortisol) concentration was positively correlated with impulsivity. The group with high post-stress cortisol also reported more symptoms of depression and anxiety, as well as self-perceived stress and stressors in every-day life. The diagnosis of ADHD significantly increased the risk of belonging to the group with high post-stress cortisol levels. The results in this study warrant a focus not only on the primary diagnosis of ADHD, but also calls for a broader assessment of stressors and subjective stress in everyday life, as well as support comprising stress management and coping skills.     

Restoring the Salivary Cortisol Awakening Response Through Nasal Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea

Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.     

Perceived stress, common health complaints and diurnal patterns of cortisol secretion in young, otherwise healthy individuals

Research has frequently linked perceived stress with changes in subjective and objective measures of ill health; however, additional assessment should consider the physiological mechanisms mediating these effects. This study investigated whether differential patterns of cortisol secretion might partially mediate perceived stress related disparities in common health complaints in young, otherwise healthy individuals. To capture the kinds of health complaints commonly reported in this population, the Pennebaker Inventory of Limbic Languidness (PILL) was selected. To capture important parameters of the diurnal profile, cortisol was sampled at waking, 30 minutes post waking, 1200 h and 2200 h on three consecutive weekdays. Results revealed flatter diurnal cortisol slopes and elevated mean diurnal output (characterised by HPA hyperactivity in the evening) for participants in the higher stress group. Participants that reported higher perceived levels of stress also reported experiencing common health complaints with markedly greater frequency; however, these disparities were abolished when mean diurnal output of cortisol was statistically controlled. While dysregulation of basal HPA activity has been implicated in the aetiologies of chronic illness, findings reported here implicated hypersecretion of cortisol as one physiological pathway, partially mediating perceived stress related disparities in the kinds of common health complaints that typically affect young, otherwise healthy individuals.     

Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones. A total of 176 subjects participated - 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05). Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations.     

Shift work parameters and disruption of diurnal cortisol production in female hospital employees

Shift work is associated with an increased risk of cardiovascular diseases (CVD). Disruption of cortisol production is a potential underlying mechanism. This study explored the associations of diurnal quantity and pattern of cortisol production in relation to (1) current shift work status (exclusive day versus rotating days and nights), (2) years of past shift work and (3) parameters of rotating shift work (timing, length and intensity). Female hospital employees (160 day workers and 168 rotating shift workers) from southeastern Ontario, Canada, participated in a cross-sectional study. Participants completed a baseline questionnaire and measures of body height, weight, and waist circumference were taken. Midstream urine samples were collected over two separate 24-hour periods to measure creatinine-adjusted cortisol. Total diurnal cortisol production and pattern were described with two measures of the area under the curve. The effect of shift work on cortisol was modeled using multivariable linear regression analyses. Cortisol production in day workers and shift workers on their day shift were similar; however, shift workers on the night shift had flatter diurnal cortisol curves and produced less cortisol. This suggests that night work is associated with an acute attenuation of cortisol production.     

Diurnal rhythm of plasma immunoreactive corticotropin-releasing factor in normal subjects

Plasma corticotropin-releasing factor (CRF), corticotropin (ACTH) and cortisol levels were simultaneously determined by radioimmunoassays at 0600 h, 1200 h, 1800 h and 2200 h in six normal subjects, in order to examine whether the diurnal rhythm in plasma CRF exists and how it correlates to the diurnal rhythm in plasma ACTH and cortisol concentration. The highest CRF level was observed at 0600 h (7.0 +/- 1.2 pg/ml) and significantly lower levels (p less than 0.01) at 1800 h (1.7 +/- 0.2 pg/ml) and 2200 h (1.9 +/- 0.4 pg/ml). A clear diurnal rhythm was demonstrated in plasma ACTH and cortisol levels, with the highest values at 0600 h (44.6 +/- 8.1 pg/ml and 15.9 +/- 2.0 micrograms/dl, respectively) and the lowest at 2200 h (12.3 +/- 2.8 pg/ml and 4.6 +/- 1.0 micrograms/ml, respectively). These results suggest that the diurnal rhythm in ACTH and cortisol is under the regulation, at least in part, of the diurnal rhythm in CRF secretion.     

Disturbance of Circadian Rhythms in Analgosedated Intensive Care Unit Patients with and without Craniocerebral Injury

Melatonin, cortisol, heart rate, blood pressure, spontaneous motor activity, and body temperature follow stable circadian rhythms in healthy individuals. These circadian rhythms may be influenced or impaired by the loss of external zeitgebers during analgosedation, critical illness, continuous therapeutic intervention in the intensive care unit (ICU), and cerebral injury. This prospective, observational, clinical study examined 24 critically ill analgo‐sedated patients, 13 patients following surgery, trauma, or acute respiratory distress (ICU), and 11 patients with acute severe brain injury following trauma or cerebral hemorrhage (CCI). Blood samples for the determination of melatonin and cortisol were obtained from each patient at 2 h intervals for 24 h beginning at 18:00 h on day 1 and ending 16:00 h on day 2. Blood pressure, heart rate, body temperature, and spontaneous motor activity were monitored continuously. Level of sedation was assessed using the Ramsey Sedation Scale. The severity of illness was assessed using the APACHE‐II‐score. The time series data were analyzed by rhythm analysis with the Chronos‐Fit program, using partial Fourier series with up to six harmonics. The 24 h profiles of all parameters from both groups of patients were greatly disturbed/abolished compared to the well‐known rhythmic 24 h patterns in healthy controls. These rhythm disturbances were more pronounced in patients with brain injury. The results of this study provide evidence for a pronounced disturbance of the physiological temporal organization in ICU patients. The relative contribution of analgosedation and/or brain injury, however, is a point of future investigation.     

Alzheimer病患者APP及PS1基因表达量的研究

为了检测Alzheimer病（Alzheimer’s disease,AD）患者外周血中淀粉样前体蛋白（Amyloid Precursor Protein, APP）基因及早老素1（Presenilin 1, PS1）基因的表达情况,进而探讨APP及PS1基因的表达与AD的相关性,采用SYBRGreenⅠ的方法对45例AD患者、25例血管性痴呆（vascular dementia, VD）患者及60名正常对照组样本的mRNA进行绝对定量,检测得到APP基因及PS1基因在对照组中的表达水平分别为0.026±0.005 amol/μg cDNA和0.026±0.004 amol/μg cDNA;在AD患者组中的表达量分别为0.044±0.006 amol/μg cDNA和0.051±0.011 amol/μg cDNA;,在VD患者组中的表达水平分别为0.072±0.013 amol/μg cDNA和0.039±0.005 amol/μg cDNA 。经显著性检验,AD患者组APP基因的表达水平上调,t=2.639, P<0.01;PS1基因的表达水平同样呈上调趋势,t=2.173,P<0.05,差异均具有统计学意义。VD患者组APP基因的表达水平上调,t=3.028,P<0.01;PS1基因的表达水平也同样呈上调趋势,t=2.012,P<0.05,均有显著性差异。因此,APP及PS1基因的表达水平的增高并不一定与AD发生特异性关联,而可能与多种导致痴呆的脑部病变发生关联。     

Phase-shifted diurnal rhythm of cortisol secretion in a patient with Cushing's syndrome due to adrenocortical adenoma

A 21-year-old woman with Cushing's syndrome was found to have a marked diurnal variation in cortisol secretion. Serum cortisol concentrations and urinary excretion of 17-hydroxycorticosteroids were normal in the morning but clearly increased in the afternoon. The patient was cured by resection of an adrenocortical adenoma. ACTH and prostaglandin E1 stimulated cortisol release from incubated adenoma tissues in vitro. The cause of the abnormal diurnal rhythm of cortisol secretion is unknown.