Adrenal plasma steroid relations in glucocorticoid-naïve premenopausal rheumatoid arthritis patients during insulin-induced hypoglycemia test compared to matched normal control females.

OBJECTIVE: Clinical and experimental data indicate the involvement of adrenal steroids in the complex of rheumatoid arthritis (RA) pathogenesis. A subtle adrenocortical hypocompetence has been suggested in a subset of glucocorticoid-naïve premenopausal females with RA. METHODS: The interrelations among adrenal steroids: cortisol (CORT), 17alpha-hydroxyprogesterone (17-OHP), androstenedione (ASD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were evaluated in 15 glucocorticoid-naïve premenopausal females with RA and in 14 age- and body mass index- matched healthy females at basal and during insulin-induced hypoglycemia states. Spearman's correlations were used to analyze baseline plasma concentrations as well as areas under response curves of these steroids levels as assayed during the basal and/or insulin-induced hypoglycemia status. RESULTS: Six among 15 RA patients, but none of 14 controls had combined "lower" quartile range of basal cortisol (< 431 nmol/l) and lower DHEAS (< 2.79 micromol/l) levels, i.e., concentrations within the lowest quartiles of the control group (p = 0.017). In all subjects combined, basal correlations were significantly positive between ASD and other steroids (CORT, 17OHP, DHEA, DHEAS). When patient and control groups were analyzed separately, the positive basal correlation between ASD and CORT was significant only in RA patients (p = 0.030). In contrast, a positive basal correlation between ASD and DHEA was significant only in controls (p = 0.004). When comparing the areas under response curves (AUCs), the correlation of ASD and CORT was significantly negative in RA (p = 0.009), but positive in controls (RA vs control difference in Spearman's correlations, p = 0.002). The correlation between AUCs of ASD and DHEA was strongly positive in controls (p = 0.006), but not in RA (RA vs. control difference p = 0.044). CONCLUSIONS: The results suggest relative hypocompetence of adrenocortical function in premenopausal RA females. Different patterns of correlations of the adrenal steroids during basal vs. stimulatory testing suggested certain alterations in adrenal synthetic pathways or deficiencies in the dynamics of steroidogenesis in RA.

Genetic predisposition to anxiety-related behavior determines coping style, neuroendocrine responses, and neuronal activation during social defeat.

Genetic background may influence an individual's susceptibility to, and subsequent coping strategy for, an acute stressor. When exposed to social defeat (SD), rats bred for high (HAB) or low (LAB) trait anxiety, which also differ in depression-like behavior, showed highly divergent passive and active coping behaviors, respectively. HABs spent more time freezing and emitted more ultrasound vocalization calls during SD than LABs, which spent more time rearing and grooming. Although the behavioral data confirmed the prediction that heightened trait anxiety would make rats more prone to experience stress, adrenocorticotropin and corticosterone were secreted to a higher extent in LABs than in HABs. In the latter, Fos expression upon SD was enhanced in the amygdala and hypothalamic areas compared with LABs, whereas it was diminished in prefrontal and brainstem areas.

Integrated neuroendocrine immune risk factors in relation to rheumatoid arthritis: should rheumatologists now adopt a model of a multiyear, presymptomatic phase?

An integrative perspective of neuroendocrine immune (NEI) and related risk factors for the onset of rheumatoid arthritis (RA) is presented, based upon studies of the long-term presymptomatic phase. Besides the recognized genetic markers and familial predisposition, multiple immunological precursors of RA have been identified many years before the clinical onset of inflammatory manifestations. Rheumatoid factors and related antibodies occur in approximately one-half of presymptomatic susceptibles. Cigarette smoking in sufficient amount and duration is a major risk factor for RA, particularly for postmenopausal-onset women and for men. In premenopausal-onset RA, subtle insufficiency of adrenal cortical function is less well recognized. In such women, cytokine imbalance may also precede inflammatory onset of RA. In males alone, multiple hormonal and cytokine correlations were found many years before the onset of RA, implying long-term activation or perturbation of this NEI system. The proposed physiopathogenetic model of RA requires further controlled, prospective studies for validation of the multiyear presymptomatic phase of RA. Such studies promise to clarify the currently unknown causal and sequential chains in this enigmatic disease.

Oxytocin in the medial amygdala is essential for social recognition in the mouse.

Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities. OT treatment fully restores social recognition. Here we demonstrate that OT acts in the medial amygdala during the initial exposure to facilitate social recognition. OT given before, but not after, the initial encounter restores social recognition in OT knock-out mice. Using c-Fos immunoreactivity (Fos-IR) as a marker of neuronal activation in this initial encounter, we found similar neuronal activation in the wild-type (WT) and OT knock-out mouse in olfactory bulbs, piriform cortex, cortical amygdala, and the lateral septum. Wild-type, but not OT knock-out mice exhibited an induction of Fos-IR in the medial amygdala. Projections sites of the medial amygdala also failed to show a Fos-IR induction in the OT knock-out mice. OT knock-out, but not WT, mice showed dramatic increases in Fos-IR in the somatosensory cortex and the hippocampus, suggesting alternative processing of social cues in these animals. With site-specific injections of OT and an OT antagonist, we demonstrate that OT receptor activation in the medial amygdala is both necessary and sufficient for social recognition in the mouse.

Initiation and frequency of pumping and milk production in mothers of non-nursing preterm infants.

This secondary data analysis examined if time of initiation of milk expression and pumping frequency influenced milk weight weeks 2-5 postpartum. Of the 39 subjects in the convenience sample, 20 were in the early initiating (EI) group, (n = 12 high frequency [HF], n = 8 low frequency [LF]), and 19 were in the late intiating (LI) group, (n = 7 HF, n = 12 LF). The EI group initiated pumping < or = 48 hours after birth; the HF group pumped a minimum of 6.25 times daily. A two-way analysis of variance indicated that milk weight was significantly higher in the HF as compared to the LF group. While there was no significant difference in milk weight between the EI and LI groups, there was a significant interaction between frequency and initiation. Milk weight for the LF/EI group appeared to be positively influenced by the initiation of mechanical expression soon after birth.

Outcome analysis of chest pain patients discharged from the ED--a pilot study.

The objective of this pilot study was to determine clinical predictors of adverse outcome, defined as myocardial infarction, angioplasy or stent placement, coronary artery bypass graft, or death, within 60 days for patients discharged from the emergency department with a presenting complaint of chest pain. All patients presenting to the emergency department with a chief complaint of chest pain were eligible for the study. A chest pain risk analysis sheet was completed as part of the patient evaluation. Patients discharged from the emergency department, in whom a risk analysis sheet was completed, were contacted to determine their clinical course within 60 days of their discharge from the emergency department. During the 6-month study period, 129 eligible patients were enrolled. Of these 129 patients, four had an adverse outcome within 60 days of their discharge. All four patients had either a balloon angioplasty procedure, coronary artery bypass graft, or both. None of the study patients had a myocardial infarction or died. Statistically significant predictors of adverse outcome in our study population were an abnormal electrocardiogram (ECG), a history of myocardial infarction, and a history of hypertension. In conclusion, patients discharged from the emergency department with a presenting complaint of chest pain were at a low risk for having a myocardial infarction or dying within 60 days of their discharge. Several patients, however, did have significant coronary artery disease requiring angioplasty or bypass. These patients were more likely to have an abnormal ECG, a history of myocardial infarction, or have a history of hypertension. A prospective study with larger numbers of patients is needed to validate these findings.

Relation of plasma oxytocin and prolactin concentrations to milk production in mothers of preterm infants: influence of stress.

Responses of oxytocin and PRL to mechanical breast pumping and the influence of physiological indicators of stress were measured at 2, 4, and 6 weeks postpartum to determine potential causes of inadequate milk production in 18 women with prematurely delivered, nonnursing (<1500 g) infants. Median milk production was similar to that reported in breastfeeding mothers, but a third of mothers were producing less than half as much by week 6. Plasma oxytocin was similar to that previously reported for breastfeeding mothers. The oxytocin area under the curve (AUC) for breast-pumping sessions (70 min) was correlated at each occasion (r = 0.37, 0.58, and 0.55, respectively) with milk yield. Unlike reports of PRL levels in breast-feeding women, PRL AUC declined between weeks 2 and 6 weeks postpartum (P = 0.03); significant increases in plasma PRL occurred in response to pumping at 2 and 4 weeks, but not at 6 weeks. Salivary amylase, a measure of alpha-adrenergic activity, was highly negatively correlated on each occasion with PRL AUC (r = -0.58, -0.68, and -0.86, respectively), but not with oxytocin. Salivary cortisol was negatively correlated to a lesser degree. We hypothesize that deficiencies in preterm lactation are mediated in part upon stress-induced suppression of PRL secretion through an adrenergic mechanism.

Fibromyalgia in men: comparison of clinical features with women.

OBJECTIVE: To describe possible differences between male and female patients with fibromyalgia syndrome (FM) in their clinical manifestations. METHODS: Five hundred thirty-six consecutive patients with FM (469 women, 67 men) seen in a university rheumatology clinic and 36 healthy men without significant pain seen in the same clinic were included in the study. Data on demographic and clinical features were gathered by a standard protocol. Tender point examination was performed by the same physician. Level of significance was set at p < or = 0.01. RESULTS: Several features were significantly (p < or = 0.01) milder or less common among men than women, including number of tender points (TP), TP score, "hurt all over," fatigue, morning fatigue, and irritable bowel syndrome (IBS). The total number of symptoms was also fewer among men and approached significance (p = 0.02) by parametric test, but reached significance (p = 0.001) by nonparametric analysis. All clinical and psychological symptoms as well as TP were significantly (p < 0.01) more common or greater in male patients with FM than healthy male controls, with the exception of IBS (p = 0.03). Patient assessed global severity of illness, Health Assessment Questionnaire disability score, and pain severity were similar in both sexes. CONCLUSION: Male patients with FM had fever symptoms and fewer TP, and less common "hurt all over," fatigue, morning fatigue, and IBS, compared with female patients. Stepwise logistic regression showed significant differences between men and women in number of TP (p < 0.001).

Adrenal androgen and glucocorticoid dissociation in premenopausal rheumatoid arthritis: a significant correlate or precursor to onset?

Controlled studies of adrenal steroids in premenopausal women with rheumatoid arthritis (RA) have revealed subtle and inconsistent decreases in glucocorticosteroid (GCS) function, but prominent deficiencies of adrenal androgens (AA). Such findings have suggested that hypoandrogenicity may predispose to RA in younger women. However, recent prospective studies of serum cortisol and dehydroepiandrosterone sulfate (DHEAS) levels before (x = 12 yrs) the onset of the disease (pre-RA) offer an alternative perspective. Significant dissociation of serum cortisol and DHEAS levels was found only in the subgroup of premenopausal women who developed RA before age 50. This subgroup alone had significant deficiency in serum DHEAS levels. Aggregate data imply that the documented deficits of DHEAS (and other AA) in such young females are a correlate of relative adrenal insufficiency, and that subtle GCS dysfunction may either contribute to development of RA in such young women as well as pubertal girls or may predispose to earlier onset of disease.

Effects of pumping style on milk production in mothers of non-nursing preterm infants.

Milk production was examined in 39 lactating mothers of non-nursing preterm infants from 2 tertiary care centers. The purposes of this study were (1) to compare milk production of those using sequential single (SEQ) or simultaneous double (SIM) breast-pumping regimen, and (2) to examine the relationship of selected variables to inadequate (< 3500 g/week) and adequate (> or = 3500 g/week) milk production. In multivariate analysis, mothers using SIM produced a similar amount of milk by weight during weeks 2 to 5 postpartum compared to those using SEQ. A logistic regression model including frequency of kangaroo care, frequency of pumping, high versus low income, and previous breastfeeding experience was predictive of mothers producing adequate versus inadequate milk volume 79% of the time. All of the mothers producing > 3500 g at week 2 produced adequate amounts of milk at weeks 4 and 5. None of the mothers producing < 1700 g at week 2 reached adequate production by weeks 4 and 5. Of the remaining mothers who produced 1700 g to 3500 g at week 2, 54% achieved adequate production during weeks 4 and 5 postpartum.

Perturbations of hypothalamic-pituitary-gonadal axis and adrenal androgen functions in rheumatoid arthritis: an odyssey of hormonal relationships to the disease.

Rheumatoid arthritis (RA) is a heterogeneous disease with a diverse spectrum of manifestations and course of illness. Multiple factors are believed to contribute to its etiology. Nevertheless, consistent features are observed across populations, which include (1) increased familial or immunogenetic risk in younger-onset disease; (2) female predisposition, particularly during child-bearing ages; (3) predictable clinical improvement during pregnancy and worsening postpartum; and (4) increased incidence with aging, which suggest that hormonal factors influence the disease. In 1974, serum was prospectively obtained from pre-RA cases, 4 to 20 (mean = 12.0) years prior to onset of disease and concurrently from controls (CN) matched (4 CN per 1 RA) on age (+/- 2 years), race (all Caucasians), and entry menopausal status (EMS). CN have no known rheumatic disease. Pre-RA were divided into subgroups, according to EMS, i.e., premenopausal vs. non-premenopausal (peri- or post-menopausal), and either age at entry in 1974 or age at onset of RA. For example, one 3-way subgrouping includes: I. Entry premenopausal and RA onset < age 50 years; II. Entry premenopausal and RA onset age 50+ years, and III. Entry postmenopausal. The 11 youngest pre-RA (I) had a mean entry age of 29 years and RA onset of 41 years. An alternative 4-way subgrouping (a, b, c, d) divided the female subjects into premenopausal (last menstrual period [LMP], 0-31 days) and non-premenopausal major groups, as well as younger vs. older subgroups within the major EMS categories. The younger premenopausal women in each subgrouping system, that is, I or a, overlap almost entirely. Assays (RIA) of the major sex hormones were performed, e.g., luteinizing hormone (LH); follicle stimulating (FSH); estradiol (E2); progesterone (P4); and total testosterone (T); as well as adrenal hormones, including androstenendione (A4); dehydroepiandrosterone (DHEA); its sulfate (DHEAS); and cortisol (C). A significantly lower entry mean serum DHEAS level (mumol/L) was found in the pre-RA subgroup I, than in the 43 CN (2.14 +/- 0.47 vs. 3.62 +/- 0.37, respectively, (p = 0.033). The 25 older pre-RA and 100 CN (subgroups II and III) showed close mean DHEAS levels (1.89 +/- 0.30 and 1.94 +/- 0.14, respectively, p = 0.45). The serum DHEAS levels in pre-RA vs. CN subgroups were validated in a second reference laboratory. Also, the youngest pre-RA subgroup (I) showed a significant dissociation between entry serum DHEAS and cortisol levels (r = -0.660, p = 0.027), which differed (p = 0.017) from its matched CN, and from the older pre-RA (p = 0.004). Analyses of results based upon subgroupings by EMS and entry age (a, b, c, d) showed similar results. No significant differences were found between pre-RA and CN groups in levels of serum cortisol, other adrenal steroids, or the sex hormones assayed. In a sample of younger premenopausal women, significantly low serum DHEAS levels were found 4 to 20 years prior to onset of RA. Dissociation of serum cortisol and DHEAS levels was also found in the youngest, but not older, pre-RA subjects. The data suggest that subtle adrenal cortical dysfunction, manifested mainly by adrenal androgen (AA) deficiency, may either predispose to younger-onset RA or be a long-term marker in a minority subgroup of women.

Serum prolactin in breastfeeding: state of the science.

Prolactin is one of two major hormones involved in lactation. While the role of infant suckling and oxytocin in the lactation process are well understood, the role of prolactin is less clear. A variety of factors related to prolactin have been investigated, and these are used as an organizing framework for this article. Factors include pregnancy, lactation, nursing frequency, prior lactation experience, milk production, and pharmacologic agents. The literature, while substantial in amount, presents inconsistencies. Implications for practice are discussed.

Breastfeeding experience and milk weight in lactating mothers pumping for preterm infants.

BACKGROUND: Research about parity or breastfeeding experience and its relationship with milk production in humans is limited. The purpose of this study was to determine if any difference in milk volume occurred among mothers with and without breastfeeding experience who used either a single or double breast pumping regimen the first 5 weeks postpartum. METHODS: A convenience sample of 39 mothers of nonnursing preterm infants participated from two tertiary care centers in the midwestern United States. The sequential single pumping group consisted of 20 mothers, 7 of whom had previous breastfeeding experience; the simultaneous double pumping group consisted of 19 mothers, 2 of whom had previous breastfeeding experience. Income and pumping group regimen were used as blocking variables, and average frequency of kangaroo care per week and average frequency of breast pumping per week were covariants in the repeated measures analysis of variance. RESULTS: Mothers with previous breastfeeding experience had greater milk weights over time, but weights were not significantly different when compared with those mothers with no previous breastfeeding experience. Additional analysis with the covariants of pumping frequency and kangaroo care, and with the independent variables of group, breastfeeding experience, and income resulted in statistically significantly greater milk yield in the women with previous breastfeeding experience. CONCLUSIONS: The findings of the two repeated analyses indicated the complexity of the milk production response, and the importance of considerations of environmental as well as physiologic factors.

Effects of parity and weaning practices on breastfeeding duration.

The purpose of this project was to examine (a) patterns of breastfeeding and (b) duration with parity and breastfeeding experience, and (c) mothers' reasons for termination of breastfeeding. A convenience sample of 120 breastfeeding mothers was followed by home visits and telephone for 20 weeks after delivery. The sample consisted of 69 primiparas, 40 multiparas with previous breastfeeding experience, and 11 multiparas with no prior breastfeeding experience. Parity was not significantly associated with the continuation of breastfeeding but there was a trend toward a difference made by breastfeeding experience. Inadequate milk supply and employment were the two most common reasons reported for weaning. Implications for support in the workplace and for first-time breastfeeding mothers are discussed.

Early identification of cerebral palsy using a profile of abnormal motor patterns.

OBJECTIVE: To determine whether a profile of abnormal motor patterns can identify children with cerebral palsy (CP) in the first year of life. METHODS: The Early Motor Pattern Profile (EMPP) consists of 15 items reflecting variations in muscle tone, reflexes, and movement that have been organized into a standardized format to provide the clinician with an objective picture of neurologic status. A three-point scoring system was applied to each item, delineating a clearly normal response from a clearly abnormal one and placing all partial or inconsistent responses in the middle. Twelve hundred forty-seven high-risk infants who were enrolled in a neonatal intensive care unit follow-up program were examined at 6 and/or 12 months' corrected age using the EMPP. These infants were followed to at least 36 months of age to distinguish those with CP from those with normal motor outcome or minimal impairment (no CP). RESULTS: Predictive validity of the EMPP at the 6- and 12-month examinations was determined using various pass-fail cutoffs. The optimal cutoff score at 6 months was between 9 and 10, at which the positive predictive value was 89.4, sensitivity was 87.1, and specificity was 97.8. The optimal cutoff score at 12 months was between 3 and 4, at which the positive predictive value was 91.0, sensitivity was 91.5, and specificity was 97.9. CONCLUSIONS: The EMPP offers the clinician an effective instrument to identify children in the first year of life who are at greatest risk for the development of CP. The EMPP can be incorporated into a routine health maintenance visit, adding only a few minutes to the process, and has high sensitivity and specificity.