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Biomedical subjects

R T Chatterton

Publications and source records attributed to R T Chatterton.

At least 19 recordsLinked to original sources
PubMed2005

The local hormonal environment and related biomarkers in the normal breast.

Recent developments in breast epithelial sampling techniques (nipple fluid aspiration, ductal lavage, and random fine needle aspiration) provide new opportunities for the acquisition of hormonal and cellular biomarker data in asymptomatic women, and thereby the possibility of developing a unified vision of how the hormonal environment of the breast may interact with the cellular expression of proteins, and with other evolving candidate markers of breast cancer risk. The purpose of this review is to integrate available information regarding cellular and breast fluid biomarkers of hormone action on the breast, to identify candidate biomarkers for studies of breast cancer risk and prevention. These include the estrogen receptors alpha and beta, markers of proliferative and apoptotic response, and protein markers of estrogen action in breast cells and nipple fluid. Studies of breast hormone levels in nipple aspiration fluid (NAF) show that estrone sulphate is present in large quantities in the normal breast, while the differences in serum ovarian steroids that are seen in pre- and postmenopausal women are blunted in NAF. The variability of several estradiol precursors in NAF over time is relatively small, a useful attribute of potential biomarkers of breast cancer risk, particularly if they are reversible with intervention in Phase 2 prevention trials. These studies are already providing new insights into the hormonal etiology of breast cancer, and should lead to the identification of robust, reversible biomarkers for use in breast cancer prevention studies.

Breast↗
PubMed2001

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.

Adult↗
PubMed2001

Saliva as a medium for investigating intra- and interindividual differences in sex hormone levels in premenopausal women.

Repeated measurement of ovarian steroids in saliva could provide an advantage in studies estimating long-term sex steroid exposure in premenopausal women, by reducing the measurement error associated with collection of serum or urine samples. We previously reported on characteristics of ultrasensitive RIAs adapted for extraction-free measurement of estradiol (E2) and progesterone (PG) in saliva. The purpose of the present study was to evaluate the consistency of E2 and PG levels in saliva in the same women across menstrual cycles, and to compare this with the variation observed between women. We also evaluated the effect of altering the number of consecutive daily samples considered and the method for locating a particular cycle day in relation to ovulation (day 0). Study participants included 12 healthy women who provided daily saliva samples for two consecutive, ovulatory menstrual cycles. A single midluteal serum sample was collected 7-8 days after detection of a luteinizing hormone (LH) peak in urine. We plotted individual cycle profiles and computed intraclass correlation coefficients (ICC) for various definitions of peak and cumulative daily hormone level. For peak PG, determined as the maximal running 3-day mean, ICC was 0.68. For cumulative PG, based on 8 consecutive cycle days (+2 to +9), ICCs were 0.72-0.76 when reverse dating LH peak or rise in salivary PG determined day 0. For E2, ICCs ranged from 0.74 to 0.79 by various dating methods for the 5 preovulatory days (-4-0), and from 0.85 to 0.92 for the 15 days about the center of the cycle (-6 to +8). With exclusion of just the first 5 days of the cycle, the ICC for E2 was 0.91. For both E2 and PG, selection of 5 or 7 days for the estimation of the midluteal mean level provided separation of within and between subject variance that was comparable with a LH-timed serum sample. These results indicate that daily saliva samples can be combined to clarify the interindividual differences in E2 and PG levels in premenopausal women, and that these interindividual differences may be greater than previously imagined.

Adult↗
PubMed2000

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.

Adrenal Glands↗
PubMed2000

Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress.

Two of the most salient physiological responses to stress are increased norepinephrine (NE) and cortisol (CORT) activities. However, it is unclear how these neurochemical events affect cognition, especially attention. We examined the effects of mild psychological stress on selective attention, as assessed by the negative priming (NP) paradigm. Salivary measures of the stress hormone CORT and alpha-amylase (a correlate of NE) were assayed to probe the relationship between the stress response and attentional inhibition. Healthy subjects (N = 20) engaged in the attention task, which was then followed by 15 min of a stressful video game before a return to the attentional task. Baseline saliva samples were obtained before the experiment began, 1 min after the video-game stressor, and 20 min post-stress. Subjects showed a significant reduction in NP and a decrease in reaction time (RT) after the video game. Moreover, alpha-amylase levels increased significantly after the stressor, indicating the role of NE in the acute stress response. While CORT levels remained unchanged after stress, CORT correlated significantly with both NP scores and RT after the stressor. These results imply that mild psychological stress can significantly alter attentional processes. Given the increase in alpha-amylase and the correlation between attention and CORT after stress, it seems likely that attentional processes are under tight control by brain systems which mediate the fight-or-flight response.

Adolescent↗
PubMed2000

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.

Adult↗
PubMed1999

Growth factors in expressed prostatic fluid from men with prostate cancer, BPH, and clinically normal prostates.

BACKGROUND: Although growth factors such as epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, and TGF-beta are important regulators of prostate cell growth in vitro and in animal models, evidence to support their role in human prostate cancer development remains sparse. We previously showed that men without prostate cancer have concentrations of EGF and TGF-alpha in expressed prostatic fluid (EPF) that are individually distinct and stable over time. This study addressed whether growth factor levels in EPF are associated with the presence or progression of prostate cancer. METHODS: We measured levels of immunoreactive EGF, TGF-alpha, and TGF-beta1 in stored EPF samples from three age-matched groups: 19 men with untreated, histologically diagnosed prostate cancer (CaP), 38 with benign prostate hyperplasia (BPH), and 19 with normal prostate glands (NPD). RESULTS: Median TGF-alpha was lower in the BPH group (0.45 ng/ml) than in either CaP (0.63 ng/ml) or NPD (0.58 ng/ml) groups (P = 0.03 and 0.12, respectively). For EGF, the median was lowest in the CaP group and highest in the NPD group (92.5 ng/ml vs. 175.5 ng/ml, P = 0.006). For TGF-beta1, the median level in CaP was 2.7 times higher than the median level among all controls (6.65 ng/ml vs. 2.46 ng/ml, P = 0.002). Growth factor levels were not associated with tumor stage or Gleason score. However, the single case with distant metastases had TGF-beta1 levels 23-fold higher than the CaP median. CONCLUSIONS: The results suggest that at the time of CaP diagnosis, EGF levels in EPF are significantly lower, and TGF-beta1 levels significantly higher, than normal. Marked overexpression of TGF-beta1 in advanced CaP might be reflected in extremely high EPF levels.

Aged↗
PubMed1999

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.

Adrenal Glands↗
PubMed1999

Salivary estradiol and progesterone levels in conception and nonconception cycles in women: evaluation of a new assay for salivary estradiol.

OBJECTIVE: To determine the usefulness of salivary E2 and progesterone for noninvasive assessment of ovarian function. DESIGN: Prospective study of salivary hormone levels in women planning a pregnancy. SETTING: Department of Obstetrics and Gynecology at Northwestern University Medical School in Chicago, Illinois. PATIENT(S): Fourteen women aged 23-39 years with regular menstrual cycles who were planning a pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Salivary estradiol and progesterone concentrations. RESULT(S): The sensitivity of the E2 assay is 2.0 pmol/L; the interassay coefficient of variation was 5.2% (mean value 17 pmol/L). Recovery of E2 added to saliva was 106%. The correlation with simultaneous serum samples was 0.71. Menstrual cycle patterns contained a preovulatory depression and a midcycle surge. By comparison with nonconception cycles, the luteal phases of conception cycles had significantly elevated salivary E2 within the first 5 days after ovulation. Salivary progesterone was significantly elevated but not until 10 days after ovulation. CONCLUSION(S): Salivary measurements of E2 and progesterone can be used as noninvasive methods for assessment of ovarian function. Salivary specimens can be collected at home and brought to the laboratory for analysis, obviating the need for frequent phlebotomy. The sensitivity and precision of the salivary E2 assay make it comparable with assays of serum E2 for assessing changes in hormone levels.

Adult↗
PubMed1999

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.

Adolescent↗
PubMed1999

Serum levels of total and free IGF-I and IGFBP-3 are increased and maintained in long-term training.

The goals of this study were to determine whether the long-term training regimens experienced by competitive collegiate swimmers would result in altered levels of total and free serum insulin-like growth factor I (IGF-I) as well as IGF-binding proteins (BP) IGFBP-1 and -3. Two male (Teams 1M and 2M) and one female (Team 2F) teams were studied at the start of training, after 2 mo of training, after 4 mo (2-4 mo had the highest volume of training), after 5 mo (near the end of tapering; only for Team 1M), and several days after training was over. For Team 1M, total IGF-I concentrations were increased by 76% after 4 mo and were subsequently maintained at this level. Total IGF-I responses were more variable for Teams 2F and 2M. Free IGF-I levels were increased nearly twofold for all teams at 2 mo and were maintained or increased further with subsequent training. Only the levels of free IGF-I for Team 1M returned to pretraining values after training had ended. Training had little effect on IGFBP-1 levels. For all teams, serum IGFBP-3 was elevated by 4 mo of training (for Team 2F it was increased at 2 mo) by 30-97% and remained at these higher levels thereafter. The ratio of total IGF-I to IGFBP-3 was not increased by training in any group. These data indicate that serum levels of total and free IGF-I and total IGFBP-3 can be increased with intense training and maintained with reduced training (tapering). The findings show that changes in free IGF-I levels are not accounted for by alterations in the total IGF-I/IGFBP-3 complex or in IGFBP-3 levels and indicate that there are other important determinants of free IGF-I.

Adolescent↗
PubMed1999

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.

Adult↗
PubMed1999

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.

Breast Feeding↗
PubMed1999

Breast cancer risk factors in two distinct ethnic groups: Indian and Pakistani vs. American premenopausal women.

Asian Indians from the Indian subcontinent have low rates of breast cancer, but studies on breast cancer risk factors in Indian and Pakistani women living in the United States are lacking. This study contrasted breast cancer risk factors [serum total 17 beta-estradiol (E2), sex hormone-binding globulin-bound E2, available E2, estrone (E1), and dehydroepiandrosterone sulfate, reproductive history, family history of cancer, body composition/size, dietary intake, physical activity, and excretion of isoflavones] between two distinct ethnic groups of premenopausal women residing in the United States. We also determined the contribution of these and other factors to the variability of each sex hormone. Distributions of values for serum total E2, available E2, and sex hormone-binding globulin-bound E2 (%) were greater (p < 0.005) in American (n = 47) than in Indian and Pakistani (n = 47) women. Multiple regression analysis indicated that 26% of the variability (p < or = 0.0001) in serum E2 was accounted for by the ratio of total cholesterol to high-density-lipoprotein cholesterol, length of time in the United States, and saturated fat intake, whereas less (17%) variability was accounted for by available E2 (representing free E2 + albumin-bound E2), contributed by the ratio of total cholesterol to high-density-lipoprotein cholesterol and saturated fat intake. Five variables accounted for 31% of the variability (p < or = 0.0001) in E1. The major finding of this study was that circulating sex hormone concentrations were determined more by environmental factors than by ethnicity, which was not a significant contributor to any of the serum hormones.

Adult↗
PubMed1997

Strategies for ovulation induction and oocyte retrieval in the lowland gorilla.

PURPOSE: Ovulation induction and oocyte retrieval were performed in a lowland gorilla in an attempt to propagate and potentially cryopreserve embryos from an infertile animal and to advance techniques to help preserve this endangered species. RESULTS: Following 34 days of leuprolide acetate suppression, human menopausal gonadotropins were administered for 14-days in a 32-year-old wild-born lowland gorilla. Ten oocytes were retrieved by transrectal ultrasound-guided aspiration. Other approaches to oocyte recovery were not feasible in this case. A serum estradiol concentration of 4700 pg/ml at the time of human chorionic gonadotropin administration did not induce ovarian hyperstimulation. Mature oocytes were recovered from follicles measuring 14 to 24 mm in diameter, with a corresponding average serum estradiol concentration of approximately 300 pg/ml for each mature follicle. Cryopreservation of a gorilla embryo was effected from cryopreserved gorilla spermatozoa. CONCLUSIONS: Parameters for monitoring ovulation induction in the gorilla appear to be similar to those for humans. The results indicate that the use of a gonadotropin releasing hormone agonist and higher doses of gonadotropins than previously used in gorillas appear to improve oocyte recovery.

Animals↗