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Biomedical subjects

R Chatterton

Publications and source records attributed to R Chatterton.

At least 19 recordsLinked to original sources

The effects of PCB exposure and fish consumption on endogenous hormones.

Previous studies have suggested that exposure to polychlorinated biphenyls (PCBs) may alter thyroid function, but data on effects of PCB exposure on other endogenous hormones has been lacking. The current study is ancillary to a larger investigation of the effects of Great Lakes fish consumption on PCBs and reproductive function. In the current study we examine associations of PCBs, 1,1-bis (4-chlorophenyl)-2,2-dichloroethene (DDE), and fish consumption with thyroid and steroid hormones in 178 men and PCBs, DDE, and fish consumption with thyroid hormones in 51 women from the original study. Serum PCB level and consumption of Great Lakes fish are associated with significantly lower levels of thyroxine (T(4)) and free thyroxine index (FTI) in women and with significantly lower levels of T(4) in men. Fish consumption, but not PCB level, is significantly and inversely associated with triiodothyronine (T(3)) in men. Results for thyroid-stimulating hormone (TSH) are inconsistent. Among men, there are significant inverse associations of both PCB and fish consumption with sex hormone-binding globulin (SHBG)-bound testosterone, but no association with SHBG or free testosterone. There are no significant overall associations of PCB, DDE, or fish consumption with estrone sulfate, follicle-stimulating hormone, luteinizing hormone, or dehydroepiandrosterone sulfate. The results of this study are consistent with previous studies showing effects of fish consumption and PCB exposure on thyroid hormones and suggest that PCBs may also decrease steroid binding to SHBG. Elucidation of specific mechanisms must await future investigations.

Adult↗

Suicides in an Australian inpatient environment.

Associated stressful life events both within and outside the hospital environment may contribute to the high-risk environment. The cohort studied here was hospitalized for a significant psychiatric problem, a factor which puts them in the high-risk category. When the severe psychiatric diagnosis is combined with a significant stressful life event, the risk of suicide is increased significantly.

Adult↗

Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth.

BACKGROUND: Tamoxifen has been shown to promote the growth of human endometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifene, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure antiestrogen, are two new antiestrogens being developed for the treatment of breast cancer. The effects of these drugs on endometrial cancer are currently unknown. Our objective was to evaluate the effects of toremifene and ICI 182,780 on the growth of human endometrial cancer in athymic mice. METHODS: Athymic, ovariectomized mice were implanted with human endometrial tumors and treated with estrogen, tamoxifen, or the new antiestrogens. RESULTS: The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometrial tumors in athymic mice were not substantially different. ICI 182,780 inhibited the growth of tamoxifen-stimulated endometrial cancer, in both the presence and the absence of estrogen. CONCLUSIONS: Toremifene and tamoxifen produce identical effects in our endometrial cancer models. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In contrast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, both in the presence and in the absence of estrogen, suggesting that this drug may be safe with regard to the endometrium, even if it is used following tamoxifen, and that it may not result in an increased incidence of endometrial cancer. Indeed, it is even possible that ICI 182,780 may prove useful as an adjuvant agent in early stage endometrial cancer.

Animals↗

Stress and anxiety do not result in pregnancy wastage.

The association between stress and reproductive outcome is unclear. In-vitro fertilization (IVF) is psychologically stressful and has been shown to alter psychological markers such as cortisol, prolactin and progesterone. This study was designed to assess prospectively psychological and physiological markers of stress and to determine if they are related to pregnancy outcome. Forty patients were recruited from Northwestern Medical Faculty Foundation (Chicago, Illinois, USA) having obtained an initial positive beta-human chorionic gonadotrophin (HCG) concentration 13 days after IVF with uterine embryo transfer. Patients underwent psychological and hormonal testing on three separate occasions (13, 20 and 27 days after embryo transfer) early in pregnancy. All subjects were followed to delivery. An adverse outcome was defined as a miscarriage before or after cardiac activity (including vanishing twin) or a loss before 20 weeks gestation. There was no difference in age, duration of infertility, diagnosis between patients experiencing an adverse pregnancy outcome (n = 18) and those that did not (n = 22). All patients were found to have high stress levels although this did not differentiate between groups of patients. There was no difference in hormonal markers of stress between patients. In conclusion, there is little association between psychological scores and physiological stress hormone concentrations. Also, it does not appear that high levels of anxiety and stress result in an adverse pregnancy outcome.

Adult↗

Methodologic issues in the measurement of oxytocin in human neonates.

Oxytocin's (OT) role in the onset and maintenance of labor and in the letdown reflex is well known. OT also has been recognized as a neurotransmitter having functions in the central nervous system, including an influence on behavior (e.g., initiation of maternal behavior). This research was conducted to (1) evaluate whether human tactile contact in the human newborn would increase urine OT levels and alter infant behavioral state, and (2) determine the reliability of measuring OT in human infant urine. Although the data did not support the hypotheses, it was noted that OT levels significantly decreased in infants who cried during the study period and that there was no correlation between infant's chronologic age and OT levels. The findings illustrate several methodologic and measurement problems in the study of OT in human infants and that urine sampling in the neonate is not the most reliable method to evaluate change in OT levels. Some general issues concerning research with human infants also are discussed. Further research is recommended to document baseline levels of OT in neonates and to explore the use of salivary OT to measure short-term responses to interventions.

Crying↗

Epidermal growth factor-related peptides in human prostatic fluid: sources of variability in assay results.

BACKGROUND: Prostatic fluid (PF) provides a unique medium for noninvasive evaluation of critical growth and differentiation signals in the prostatic microenvironment. The purpose of this study was to establish the feasibility of measuring two prostatic mitogens, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) in PF, and specifically to quantify extraneous variability attributable to the assay itself, sample handling, or biological variation within an individual over time. METHODS: PF was collected by transrectal massage from consecutive patients attending a urology clinic. Pooled PF and individual samples from 25 men with stable benign prostatic hyperplasia (BPH) were analyzed for EGF and TGF-alpha by radioimmunoassay and for total protein. RESULTS: Reproducibility was adequate at dilutions as low as 1:50 (2-microliter pooled sample) and 1:5 (20 microliters) for EGF and TGF-alpha, respectively. Results were not affected by freeze-thaw cycles, time in storage, or protease inhibition in fresh PF. EGF and TGF-alpha were detectable in 100% and 92% of individual men, with respective means of 152 and 0.2 ng/ml. Correlations between two samples obtained from the same man within 12 months were highly significant (EGF r = 0.89, TGF-alpha r = 0.71). Protein concentrations were consistent over time; expression of either peptide per weight of protein rather than per volume did not improve within-man correlation. Between-man variability far exceeded within-man variability for both peptides, and was estimated to account for 84% and 61% of the total variability in EGF and TGF-alpha, respectively. There was no correlation between EGF and TGF-alpha in the same samples. CONCLUSIONS: We conclude that men with BPH secrete consistent and distinct levels of EGF-related peptides in PF, and that these levels can be detected with acceptable sensitivity and precision by radioimmunoassay (RIA). Measurement of TGF-alpha, which has not been reported previously, requires a relatively larger sample.

Analysis of Variance↗

Eosinophilia after commencement of clozapine treatment.

OBJECTIVE: While clozapine-associated agranulocytosis has received extensive attention, a number of recent publications have identified that the incidence of eosinophilia may also be of concern. This retrospective review identifies the incidence of eosinophilia within a group of people commencing clozapine at a large hospital in Australia. METHOD: The pathology reports of all people (n = 160) who commenced clozapine within a 3.5-year period were retrospectively reviewed for incidences of eosinophilia. RESULTS: The incidence of eosinophilia was identified as 13%, comprising 17 males and four females. All cases of eosinophilia developed within 4 weeks of commencing clozapine. One male reached a peak eosinophil level of 9 x 10(9)/L, which resolved after clozapine was withdrawn. In all other cases, the eosinophilia resolved without intervention. CONCLUSIONS: With a rate of eosinophilia at 13% in this population under review, and given that there have been reports of 25 cases of eosinophilic cardiomyopathy resulting in four deaths worldwide, clinicians should be alert to the incidence and sequelae of eosinophilia in people receiving clozapine treatment.

Adult↗

Mitogenic growth factors in breast fluid obtained from healthy women: evaluation of biological and extraneous sources of variability.

Peptide growth factors (GFs), including epidermal GF (EGF) and transforming GF-alpha (TGF-alpha), are presumed to play an important role in the local regulation of breast cell proliferation. Breast fluid collected by nipple aspiration provides a potential means to assess the concentration of these factors in contact with the ductal epithelium. Although identification of immunoreactive EGF-like GFs in breast fluid has been reported previously, we performed this study to evaluate the sensitivity and reliability of newer RIA methods and to characterize the sources and amounts of both intra- and intersubject variability. We also evaluated the relationship of breast fluid EGF and TGF-alpha levels to each other and to plasma levels of estradiol and progesterone. Breast fluid and plasma samples were obtained two to four times at weekly intervals from 18 healthy, premenopausal women. EGF and TGF-alpha were measured by competitive binding RIA. Both GFs were detected with good precision in all breast fluid samples analyzed, using dilutions as low as 1:100 for EGF (1 microliter) and 1:25 for TGF-alpha (4 microliters). The correlations between the right and left breasts, sampled concurrently, were r = 0.78 (P = 0.003) for EGF and r = 0.89 (P = 0.0001) for TGF-alpha. For both GFs, the variation between women was substantially greater than the variation between breasts or over time in an individual woman, particularly for EGF, for which there were 100-fold differences between women in mean levels. When samples from multiple women were analyzed together, we found no apparent relationships between EGF and TGF-alpha levels or between either GF level and menstrual cycle phase or plasma hormone concentrations. However, in random effects analyses, EGF levels within an individual were significantly associated overall with both TGF-alpha (P = 0.02) and plasma estradiol levels (P = 0.01). These data, which are the first comprehensive results on the feasibility of measuring mitogenic GFs in breast fluid, support the conclusion that women secrete consistent and individually distinct levels of EGF and TGF-alpha and that, in at least some women, EGF secretion in vivo covaries with both TGF-alpha in breast fluid and circulating estradiol.

Adult↗

Neuroleptic malignant syndrome: an assessment of registered psychiatric nurses' knowledge.

Neuroleptic Malignant Syndrome (NMS) is a potentially fatal complication of neuroleptic use and is frequently underdiagnosed by medical and nursing staff. The current project was undertaken to assess the knowledge registered psychiatric nurses (RPN) have of the signs, symptoms and interventions to be initiated in cases of NMS. A total of 126 RPN employed in a large tertiary inpatient facility and community mental health centre responded to a self-completed questionnaire. The results indicate that while the RPN in the study's sample demonstrated adequate knowledge of NMS, there was evidence to suggest that these RPN may actually lack confidence in their ability to identify and initiate appropriate interventions in suspected cases of NMS. Although RPN employed in the rehabilitation and psychogeriatric areas of the hospital had more years of experience in the mental health field, their overall knowledge of NMS was significantly lower than that of RPN employed in other clinical settings (F = 3.35; d.f. = 5119; P = 0.007). The findings underscore the importance of ongoing education for RPN employed within clinical mental health settings.

Clinical Competence↗

Neuroleptic malignant syndrome and clozapine monotherapy.

OBJECTIVE: This report identifies neuroleptic malignant syndrome (NMS) occurring on a steady state dosage of clozapine monotherapy. CLINICAL PICTURE: An outpatient presented with a recent history of stiffness and soreness of his legs, dizziness, polydipsia, polyuria, abdominal and chest pains. After admission to a general hospital, further symptomatology was identified including: pallor, diaphoresis, nausea, confusion, agitation, decrease in normal reflexes, minimally reactive pupils and rigid limbs. TREATMENT: Intravenous (I/V) diazepam was administered but failed to decrease the agitation and confusion. He was sedated with the administered of I/V droperadol, intubated and placed on a ventilator with circulatory supports for 4 days. OUTCOME: On day five he was extubated and transfered to a medical ward. All laboratory values had returned to normal values by this time. The patient was subsequently discharged. CONCLUSIONS: Neuroleptic malignant syndrome can occur at any stage of clozapine treatment, and the patient can be rechallenged after such an episode. This person was rechallenged and after 6 months of treatment has suffered no further recurrence of NMS.

Antipsychotic Agents↗

Clozapine: exploring clients' experiences of treatment.

This paper presents the results of a case study exploring the subjective experience of Clozapine treatment in 10 clients at a major Australian psychiatric hospital. Data were categorized into: subjective improvements, observed improvements, subjective expression of concerns, side effects, and goals for the future. Responses provide direction for individualized mental health nursing care. For example, rehabilitation is ideally focused on each person's needs and goals. Such needs can best be identified by ongoing exploration of subjective and objective information.

Antipsychotic Agents↗

Clozaril. An Australian experience.

1. Clozaril, an atypical antipsychotic, did not gain approval for use in Australia until 1992. Prior to its general release, a trial was conducted in three pilot sites to test the efficacy of a monitoring system. 2. Fear of litigation among hospital staff was reduced through educational sessions that reported on the low incidence of serious side effects and the efficacy of the monitoring system. 3. The most common side effect noted with initiation of Clozaril was sedation, which persisted for 4 to 6 weeks. Subsequent side effects included drowsiness, increased salivation, and tachycardia.

Attitude of Health Personnel↗

Parasuicide in people with schizophrenia.

This paper reviews patterns of suicidal behaviour in a group of 100 people with schizophrenia. All of the people in this review have a DSM 111-R diagnosis of schizophrenia and have had contact with a clinical research unit. Fifty-four per cent of the subjects have attempted suicide. The mean number of past attempts was 2.2, with a range between 0 and 15. Within the 5 year period of the review three people have suicided. These 100 people were chosen because self-reported demographic data were available on them. The group of people who attempted suicide tended to be young, unmarried, and had higher than average rates of admission to hospital.

Adult↗

Comparison of mononuclear cell proteins and plasma proteins before and during parturition by two dimensional electrophoresis.

Two dimensional electrophoresis is a technique whereby protein sources are organized by molecular weight and electrical charge on a polyacrylamide gel. To detect changes that may be associated with the onset of parturition, we compared electrophoresis patterns of mononuclear cell proteins and plasma proteins before and during active labor. Mononuclear cells and plasma were obtained from 5 pregnant volunteers. It appears that A-1 apolipoprotein, identified by Western Blot analysis, is increased in mononuclear cells during active labor. Conversely, a decrease in the concentration of A-1 apolipoprotein was seen in plasma during parturition. These "normal" protein patterns can now be compared with those observed in pathologic conditions including preterm labor and may allow early detection of disease by protein abnormalities before clinical signs and symptoms develop.

Blood Proteins↗

Plasma estrogens, androgens, and von Willebrand factor in men on chronic hemodialysis.

The role of sex hormones in atherogenesis has not been well defined. Since hemodialysis patients show signs of feminization and an increased propensity for atherosclerosis they are particularly suited to probe the relationship between estrogen, testosterone, and atherosclerosis. Therefore, we measured plasma total, free, and protein-bound estradiol (E2), testosterone (Te), and prolactin in 28 hemodialysis patients and in 30 age-matched controls. Von Willebrand factor (vWF) levels were also assayed. Total and free E2 as well as Te were significantly decreased in the patients (p less than 0.001). However, the E2/Te ratio was elevated in the patients (p = 0.05), as was vWF (p less than 0.01). No correlations were found between hormone levels and vWF, gynecomastia or vascular disease, but vWF and vascular disease were highly correlated. We conclude that in hemodialysis patients absolute estrogen levels are lower than normal, but that the estrogen/androgen ratio is shifted in favor of estrogen because of the coexistence of androgen deficiency. These findings suggest that an elevation in the estrogen/androgen ratio, rather than an increase in estrogen per se, may be a risk factor for atherosclerosis.

Adult↗

The combined effect of quipazine and haloperidol on plasma prolactin release.

The possible dopaminergic properties of the central serotonergic agonist quipazine was examined using plasma prolactin release as a model to determine whether quipazine exerts an agonist effect on only serotonin receptors or on dopamine receptors as well. Drugs acting on two different receptors have only an additive effect on the same parameter while different drugs acting on the same receptor exert a synergistic effect. Therefore we determined whether combining quipazine with haloperidol, which has no effect on serotonin receptors, would produce a synergistic or only an additive effect on prolactin release, relative to the release induced by quipazine alone. A distinct synergism was produced, suggesting that quipazine acts on both DA and 5-HT receptors. Moreover, the model used may be useful for distinguishing whether a given drug acts on one or two receptors concurrently.

Analysis of Variance↗