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Background: A number of studies have shown that the chronic stress of caring for persons with dementia can have significant immunological consequences as demonstrated by the down-regulation/dysregulation of the cellular immune response.Methods: Utilizing flow cytometry to measure the percentages and absolute numbers of CD-4(+) and CD-8(+) T lymphocytes producing the cytokines indicative of Th-1, Tc1 and Th-2, and Tc2 cells, we compared spousal caregivers and control subjects. The expression of interleukin-2 (IL-2), interferon gamma (IFN-gamma), and interleukin-10 (IL-10) in the cytoplasm of CD-4(+) and CD-8(+) lymphocytes was assessed.Results: Neither stress nor age was significantly related to the percentage or number of IFNgamma(+)/CD-8(+), IL-2(+)/CD-8(+) cells, or IFNgamma(+), IL-2(+), CD-4(+) cells. However, the percentage of IL-10(+) cells was higher in lymphocytes obtained from caregivers than control subjects. In addition, the significant interaction between stress and aging for IL-10(+)/CD-4(+) and IL-10(+)/CD-8(+) cells demonstrated that the difference between caregivers and control subjects was age dependent; the difference between caregivers and control subjects was substantially larger in younger individuals than in older individuals.Conclusions: The data are consistent with previous reports on acute stress and suggest that there may also be a shift from a Th-1 to a Th-2 response associated with a chronic stressor such as caregiving. This shift could have implications for an individual's responses to pathogens. [ABSTRACT FROM AUTHOR]

Objective: Influenza and pneumonia account for significant morbidity and mortality, particularly in older individuals. Previous studies have shown that spousal caregivers of patients with dementia have poorer antibody and virus specific T cell responses to an influenza virus vaccine relative to noncaregiving control subjects. This study tested the hypothesis that stress can also significantly inhibit the IgG antibody response to a pneumococcal bacterial vaccine.Method: We measured antibody titers of current caregivers, former caregivers, and control subjects after vaccination with a pneumococcal bacterial vaccine.Results: Caregivers showed deficits relative to controls and former caregivers in their antibody responses to vaccination. Although the groups did not differ before vaccination or in the rise in antibody 2 weeks or 1 month after vaccination, current caregivers had lower antibody titers 3 and 6 months after vaccination than either former caregivers or controls.Conclusions: These data, the first evidence that chronic stress can inhibit the stability of the IgG antibody response to a bacterial vaccine for pneumonia, provide additional evidence of health risks associated with dementia caregiving. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that growth hormone (GH) is synthesized and secreted by human peripheral mononuclear cells (PBMC), and the expression of GH mRNA can be found throughout the human immune system.Methods: We studied a population of female caregivers of patients with Alzheimer's dementia (AD) who suffered from the stress of caring for these patients. We utilized quantitative RT-PCR to determine GH mRNA levels in T- and B-cell populations from PBMC. Subjects were nine caregivers of AD patients and nine age- and sex-matched controls.Results: In the control group we found a threefold greater GH mRNA expression in B cells than in T cells. This finding was consistent with our previous in situ hybridization observation, suggesting GH mRNA in predominately B-cell areas of immune organs in humans. We also found that the expression of GH mRNA from total peripheral blood mononuclear cells and B cells in caregivers was 50% and 60% respectively less than that in the control group.Conclusions: Because the B-cell population is the source of antibody production, our findings suggest that the decrease in B-cell GH mRNA may contribute to the poor immune response to influenza virus vaccination that has been reported previously in chronically stressed caregivers. [ABSTRACT FROM AUTHOR]

Non-insulin-dependent diabetes mellitus (NIDDM) may cause vulnerability to moderate zinc deficiency. In this study, short-term zinc supplementation (30 mg/d as amino acid chelate for 3 wk) elevated plasma zinc and activities of 5'-nucleotidase, a zinc-dependant enzyme, in 20 postmenopausal women with NIDDM. Placebo, given to 20 other women with NIDDM, had no effects on these indexes nor on any others taken in this study. Although zinc supplementation doubled the mean value for 5'-nucleotidase activity, values were still significantly lower than those of age-matched control subjects. Plasma insulin-like growth factor I concentrations increased with zinc treatment if starting concentrations were < 165 microg/L but were unchanged if they were > 165 microg/L. Lipoprotein oxidation in vitro, which has abnormal lag times and propagation rates for subjects with NIDDM and for moderately zinc-deficient rats, were unchanged by zinc supplementation. Possibly, this lack of effect occurred because the zinc treatment did not normalize zinc status. In conclusion, this study supports the contention that moderate zinc deficiency occurs frequently in subjects with NIDDM. Copyright (c) 1997 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

There is evidence that psychological stress adversely affects the immune system. We have investigated the effects of such stress, caused by caring for a relative with Alzheimer's disease, on wound healing. We studied 13 women caring for demented relatives (mean age 62.3 [SE 2.3] years) and 13 controls matched for age (60.4 [2.8] years) and family income. All subjects underwent a 3.5 mm punch biopsy wound. Healing was assessed by photography of the wound and the response to hydrogen peroxide (healing was defined as no foaming). Wound healing took significantly longer in caregivers than in controls (48.7 [2.9] vs 39.3 [3.0] days, p < 0.05). Peripheral-blood leucocytes from caregivers produced significantly less interleukin-1 beta mRNA in response to lipopolysaccharide stimulation than did controls' cells. Stress-related defects in wound repair could have important clinical implications, for instance for recovery from surgery. [ABSTRACT FROM AUTHOR]

Objective: To compare healthcare costs and utilization among participants in a study of two active lifestyle interventions implemented in the workplace and designed to foster awareness of and attention to health with a propensity score matched control group., Design and Setting: We retrospectively compared changes in healthcare (HC) utilization among participants in the mindfulness intervention (n=84) and the diet/exercise intervention (n=86) to a retrospectively matched control group (n=258) drawn for this study. The control group was matched from the non-participant population on age, gender, relative risk score, and HC expenditures in the 9 month preceding the study., Main Outcome Measures: Measures included number of primary care visits, number and cost of pharmacy prescriptions, number of hospital admissions, and overall healthcare costs tracked for 5 years after the intervention., Results: Significantly fewer primary care visits (p<.001) for both intervention groups as compared to controls, with a non-significant trend towards lower overall HC utilization (4,300.00 actual dollar differences) and hospital admissions for the intervention groups after five years. Pharmacy costs and number of prescriptions were significantly higher for the two intervention groups compared to controls over the five years (p<0.05), yet still resulted in less HC utilization costs, potentially indicating greater self-management of care., Conclusion: This study provides valuable information as to the cost savings and value of providing workplace lifestyle interventions that focus on awareness of one's body and health. Health economic studies validate the scale of personal and organization health cost savings that such programs can generate., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03) with age (R2 = -0.23), vascular stiffness (R2 = -0.24), and central aortic pressure (R2 = -0.19) and positively correlated with body mass index (R2 = 0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network. Furthermore, the coordinated gene expression in these modules can be linked to cardiovascular risk factors and subclinical cardiovascular disease; thus, this measure may be useful for their diagnosis and prognosis.

An extensive body of research defines the default-mode network (DMN) to be one of the critical networks of the human brain, playing a pivotal functional role in processes of internal mentation. Alterations in the connectivity of this network as a function of aging have been found, with reductions associated with functional ramifications for the elderly population. This study examined associations between integrity of the DMN and trait levels of mindfulness disposition, defined by our ability to exert attentional and emotional control in the present moment, and, thereby, bring awareness to immediate experiences. Twenty-five older adults participated in the study and underwent a brief functional magnetic resonance imaging session and filled out questionnaires related to their overall health and mindfulness disposition. Mindfulness disposition was associated with greater connectivity of the DMN, specifically, in the dorsal posterior cingulate cortex and the precuneus. Mindfulness disposition, thus, explains variance in the connectivity of one of the more intrinsic networks of the human brain, known to be critical for promoting self-relevant mental explorations and building cognitive and affective control.

Background: Human and animal laboratory studies have shown that stress delays healing of standardized punch biopsy wounds., Purpose: This 5-week prospective study of 17 women who underwent elective gastric bypass surgery addressed the association between postsurgical pain intensity and subsequent healing of a standard 2.0-mm punch biopsy wound., Methods: Participants were assessed 1 week before surgery, within 3 hr before surgery, 1 to 3 days postsurgery, and at weekly intervals for 4 weeks following surgery., Results: Patient ratings of greater acute postsurgical pain, averaged over Days 1 and 2 postsurgery, and greater persistent postsurgical pain, averaged over 4 weekly postsurgery pain ratings, were significantly associated with subsequent delayed healing of the punch biopsy wound. Presence of depressive symptoms on the day of surgery, pre-existing persistent pain, and medical complications following initial discharge from the hospital were not related to wound healing. Depressive symptoms on the day of surgery and pre-existing persistent pain did predict persistent postsurgical pain intensity., Conclusions: These findings extend the previous laboratory models of wound healing to a surgical population, providing the first evidence that pain plays an important role in postsurgery wound healing, a key variable in postsurgical recovery.

In this study, we measured serum prolactin (PRL), cortisol, growth hormone, interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-alpha in patients admitted with small-to-moderate burn injuries. Serum samples were obtained at the time of admission from 49 adult male burn patients with ages ranging from 18 to 91 years and TBSA ranging from 0.001 to 60%. The levels of serum PRL, IL-8, IL-6, and IL-1beta correlated positively with the TBSA, whereas only serum IL-8 levels correlated positively with fatality. Each of these factors were increased at least 2-fold at the higher burn severity. Not surprisingly, there was a large degree of variability in the hormone and cytokine levels in this patient population, which presumably reflects individual levels of stress, as well as other physiological variables. We also studied relationships between serum hormone levels and serum cytokine levels in this context. Linear regression analysis revealed a significant positive correlation between the serum PRL level and the levels of IL-10, IL-6, and IL-8. These results indicate that PRL responds to burn injury at early time points and that a subset of cytokines are involved in the early response to burn injury.

Age-related structural and functional changes in the cardiovascular, sympathoadrenomedullary (SAM), and hypothalamic-pituitary-adrenocortical (HPA) systems may affect the ability to reliably identify individual differences in response to stress. Heart rate, preejection period, respiratory sinus arrhythmia, respiratory rate, norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol were assessed in 64 healthy older women (mean = 67 years) in response to a mental arithmetic and public-speaking task. All cardiovascular and endocrine measures changed significantly during the tasks. All measures were consistent across the two tasks (r(s)s = .50 to .97). Moreover, a majority of women in this sample exhibited cross-task consistency in the relative activation of the autonomic, SAM, and HPA systems (i.e., response profiles). Further research is recommended to examine the significance of consistent individual differences in response profile.

Using sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) methods, we showed the expression of mRNA for growth hormone (GH) but not prolactin (PRL) in whole human skin (normal and basal cell carcinoma (BCC)). These RNAs for PRL and GH were below detectability in human epidermal keratinocytes and in human and hamster malignant melanocytes. This is in agreement with previous studies showing GH gene expression in dermal fibroblasts. GH peptide was not detected (by immunocytochemistry) in human skin specimens (normal and pathologic) in either dermal or epidermal compartments. The mRNA coding for the GH mediator insulin-like growth factor-1 (IGF-1) was detectable in whole skin and in malignant melanocytes. Therefore, in the present investigation of hormonal mediators of the cutaneous (epidermal) response to environmental stress, we have excluded the direct participation of PRL and GH in that reaction. Thus the analogy previously noted between the systemic (central) and skin responses to stress, as represented by cutaneous expression of hypothalamic-pituitary-adrenal axis components, does not extend to other pituitary hormones also involved in that response such as PRL and GH.

We investigated autonomic and endocrine responses to acute stressors in 27 women who were or are presently caring for a spouse with a progressive dementia (high chronic stress) and 37 noncaregivers who were category matched for age and family income (low chronic stress). Measures were taken before (low acute stress) and in response to brief laboratory stressors (high acute stress). We replicated prior research showing that caregivers report greater stress, depression, and loneliness than the comparison groups, and acute stressors elevate autonomic and neuroendocrine activity. We also found that caregivers, relative to noncaregivers, exhibited shorter preejection periods and elevated blood pressure and heart rate, but the magnitude of autonomic and neuroendocrine reactivity to the experimental stressors was comparable across these groups. This pattern of autonomic differentiation replicates prior research showing that caregivers are characterized by higher sympathetic activation than noncaregivers and suggests that the effects of chronic stress on physiological reactivity may be a less robust effect in older adults.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Background: Several recent studies have shown that stress markedly delays wound healing. This study assessed the relationship between psychological stress and the secretion of proinflammatory cytokines at an actual wound site, providing in vivo data on the development of local immune responses that are central in the early stages of wound repair., Methods: To study the dynamics of inflammation, skin blisters were induced on the forearm of 36 women (mean age, 57 years) by suction. After the blister roofs were removed, a plastic template was taped to the arm, and wells were filled with 70% autologous serum in buffer. Specimens were aspirated from blister chamber wells 5 and 24 hours after wounding., Results: Women with higher perceived stress scores demonstrated significantly lower levels of 2 key cytokines--interleukin 1alpha and interleukin 8--at wound sites. In addition, subjects who had low levels of both cytokines after 24 hours reported more stress and negative affect, and they had higher levels of salivary cortisol than those who had high cytokine levels., Conclusion: Consistent with the evidence that stress delays wound healing, these data suggest a possible mechanism: psychological stress has measurable effects on proinflammatory cytokine production in the local wound environment.

The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 micrograms octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I (IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 micrograms octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 micrograms/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 micrograms. In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 micrograms/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 micrograms daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10(3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondary treatment group) to a mean of 2.2 +/- 0.3 x 10(3) U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was observed in 6 of 13 patients, with reduction in tumor volume greater than 25% in only 3. Of 6 patients with documented tumor shrinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. (AB

Ninety newlywed couples (mean age = 25), selected on the basis of extremely stringent mental and physical health criteria, were admitted to a hospital research unit for 24 hours to provide a detailed assessment of conflict-resolution behaviors and changes in autonomic, endocrine, and immune function. Among these newlyweds, negative or hostile behaviors during marital conflict (coded from videotaped interactions) were associated with increased levels of epinephrine, norepinephrine, growth hormone, and ACTH as well as greater immunological change over the subsequent 24 hours. Wives demonstrated greater and more persistent physiological changes related to marital conflict than husbands. To assess the generalizability of these physiological changes, a similar laboratory paradigm was used with 31 older couples (mean age = 67) who had been married an average of 42 years. Consistent with the data from newlyweds, both endocrinological and immunological data showed significant relationships to negative behavior during marital conflict in these older couples. These findings suggest that abrasive marital interactions have important endocrinological and immunological correlates.

We examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. Results revealed that psychological stressors heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected the cellular immune response (ps < 0.05). In a replication and extension, 27 women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls category matched for age and family income (low chronic stress) performed the 12-min laboratory stressor. Measures were taken before (low acute stress) and immediately following (high acute stress) exposure to the laboratory stressors as well as 30 min after termination of the stressor (recovery period). Acute stress again heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected cellular immune responses (ps < 0.05), whereas chronic stress was associated with higher reports of negative affect, enhanced cardiac sympathetic activation, elevated blood pressure and plasma levels of ACTH, and diminished production of interleukin-1 beta (ps < 0.05). Correlational analyses in both studies further suggested that individuals who showed the greatest stress-related changes in HPA activation also exhibited the greatest diminution in cellular immune response.

We compared virus-specific antibody and T-cell responses to influenza virus vaccination in 32 caregivers of Alzheimer's disease (AD) patients and matched control subjects. Caregivers showed a poorer antibody response and virus-specific T-cell response following vaccination compared to the control subjects as measured by fourfold increases in antibody titers to the vaccine and lower levels of virus-induced IL-2 levels in vitro. We performed a second study in which forty-eight medical students were inoculated with a series of three injections of the hepatitis-B (HEP-B) vaccine to coincide with the third day of three, three-day examination blocks. Twelve of the 48 medical students seroconverted after the first injection; these students were characterized by falling into the lower stressed/lower anxiety group of students. Students who reported greater social support and lower anxiety and stress demonstrated a higher antibody response to the vaccine and a more vigorous T-cell response to HEP-B surface antigen at the end of the third examination experience. The differences in antibody and T-cell responses to HEP-B and influenza virus vaccinations provide a demonstration of how stress may be able to alter both the cellular and humoral immune responses to vaccines and novel pathogens in both younger and older adults.

This study investigated whether the stress of caregiving alters cellular immune responses to acute psychological stressors. Twenty-seven women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls matched for age and family income performed a 12-min laboratory stressor. Cellular immune function was assessed by both functional and quantitative measures taken before (low acute stress), immediately after (high acute stress), and 30 min after (recovery from stress) exposure to the laboratory stressors. The laboratory challenges were associated with diminished proliferative responses but elevated natural killer (NK) cell cytotoxicity; however, subsequent analyses suggested that this elevated cytotoxicity was largely attributable to an increase in the number of NK cells in peripheral blood. The results suggest that although the stress of caregiving diminishes cellular immune function, caregiving appears to have little effect on cellular immune responses to or recovery from brief psychological challenges.

'Big' and 'big-big' hyperprolactinemia, the presence of increased serum concentrations of high molecular weight (50-60 and 150 kDa respectively) prolactin forms, has mostly been reported in women with idiopathic hyperprolactinemia and normal hypothalamic-pituitary ovarian axis function. It has been suggested that both 'big' and 'big-big' prolactin species are biologically less active than the 22 kDa form predominating in normal individuals. We report the cases of two men with pituitary adenomas who were secreting significant amounts of 'big' (50-60 kDa) prolactin documented by Sephadex G-100 column chromatography. Both patients reported normal sexual function despite high prolactin levels. Results of nocturnal rigidity and tumescence testing were normal, confirming that significant hyperprolactinemia was not interfering with either patient's sexual function. 'Big' hyperprolactinemia should thus be suspected even in male patients with prolactin-secreting pituitary adenomas who maintain adequate sexual function in the presence of high prolactin levels.

We evaluated the influence of continual estrogen replacement therapy (ERT) as presently practiced by postmenopausal women with conjugated estrogens and medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and MPA). In the women receiving only conjugated estrogens, increased GH levels and decreased IGF-1 levels were found, which replicated previous research and probably reflected estrogen inhibition of hepatic IGF-1 production with a secondary increase in GH release because of reduced feedback inhibition. In women taking both MPA and estrogen, GH was increased and the previously observed estrogen induced decrease in IGF-1 levels was inhibited. In order to determine the influence of ERT on psycho-social stress-induced GH release, math (mental stress) and speech (social stress) challenges were utilized, and they produced significant increases in heart rate in all three groups. The heart rate following stress was significantly enhanced by estrogen replacement. These stressors also led to increased GH secretion in the women taking estrogen and MPA, but not in the other two groups. Gonadal steroids and GH can influence cellular immunity. We observed that ERT in both groups was associated with significantly enhanced lymphocyte responsiveness to the T-cell mitogens phytohemaglutinin (PHA) and Conconavalin A (Con A), and basal GH levels were correlated with the PHA response in the estrogen only group. ERT did not influence natural killer (NK) cell activity. We also found significant differences in the steady-state expression of latent Epstein-Barr virus (EBV) with increased antibody titers in the women in the estrogen only group and lower antibody titers in the MPA plus estrogen group. GH levels were correlated with EBV antibody titers in the estrogen plus MPA group. This study supports the hypothesis that GH and immune modulation can be influenced by ERT in postmenopausal woman. Given the extant literature on the immune-enhancing effects of GH, these data suggest that ERT may slow the decline of GH secretion with aging, an event that has been implicated in immunosenescence.

In longitudinal research investigators often measure multiple variables at multiple points in time and are interested in investigating individual differences in patterns of change on those variables. In the vast majority of applications, researchers focus on studying change in one variable at a time. In this article we consider methods for studying relations1.1ips between patterns of change on different variables. We show how the multilevel modeling framework, which is often used to study univariate change, can be extended to the multivariate case to yield estimates of covariances of parameters representing aspects of change on different variables. We illustrate this approach using data from a study of physiological response to marital conflict in older married couples, showing a substantial correlation between rate of linear change on different stress-related hormones during conflict. We also consider how similar issues can be studied using extensions of latent curve models to the multivariate case, and we show how such models are related to multivariate multilevel models.

"Pituitary" peptides are produced in both endocrine and immune cells. Acute and chronic stress can alter pituitary peptide secretion and might also influence neuroendocrine gene expression in human immune cells. We reasoned that, in Alzheimer caregivers, the chronic stress of caregiving would impact on the sympathetic-adrenal-medullary and hypothalamicpituitary-adrenal axis possibly leading to alterations in GH mRNA in their peripheral blood mononuclear cells (PBMCs). Therefore, we evaluated 10 caregivers and 10 controls subjects using a math and speech stress protocol to determine their neuroendocrine profile and to evaluate any relationship with mononuclear cell GH mRNA levels simultaneously acquired and then evaluated by a quantitative competitive RT-PCR technique. We found a significant (p<.0001) decrease 50% in GH mRNA levels in cells from caregivers. Plasma ACTH and norepinephrine levels were negatively correlated with GH mRNA levels, suggesting their possible role in the down-regulation of mononuclear cell GH gene expression. These observations support the hypothesis that experiences associated with caregiving alter the brain's autonomic nervous system and neuroendocrine control of the hypothalamic-pituitary axis. These and perhaps other influences may then produce altered GH gene expression in mononuclear cells of chronically stressed individuals. It is tempting to speculate that the decreased GH mRNA that we found in these chronically stressed caregivers was partially responsible for their poor response to influenza vaccine and their delayed wound healing.

Idiopathic hyperprolactinemia can be found in men with either normal or low serum testosterone (T) levels. The explanation for the differing effects on T of similar PRL levels has not been found. Macroprolactinemia, as a clinical entity, has been reported mostly in women. These macromolecules are biologically less active and/or are transported less easily across the capillary bed than the 22-kDa molecules. Therefore, women with elevated PRL levels retain normal menses and fertility. We studied six men, aged 28-53 yr (mean, 45 yr), in whom hyperprolactinemia was initially considered to be the cause of their erectile dysfunction. PRL levels ranged from 25-92 ng/mL (normal, 2-15 ng/mL), but T and gonadotropin levels were normal, suggesting that PRL was not disrupting gonadotropin and gonadal steroid function. The results of magnetic resonance imaging studies of the pituitary gland were normal. Separation by Sephadex G-100 column chromatography showed a predominance (85-90%) of big (60 kDa) and big big ( > 150 kDa) PRL, in contrast to the predominance of 22-kDa PRL in normal subjects. Nocturnal tumescence testing was normal, supporting the diagnosis of psychogenic impotence in these subjects, and potency returned after counseling. Hence, the biologically inactive macroprolactinemia did not cause any organic derangement in erectile function. It further obscured and delayed the appropriate diagnosis and treatment of these individuals.