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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 451 records · Page 25Linked to original sources
PubMed1998

Care staff responses to people with learning disabilities and challenging behaviour: a cognitive-emotional analysis.

This study explores the application of Weiner's cognitive-emotional model of helping behaviour to care staff responses to challenging behaviour of people with learning disabilities. Participants were 20 residential care staff who worked with people with challenging behaviour and 20 who did not. Six examples of challenging behaviour were presented, and for each behaviour participants were asked to give a probable cause, rate attributions of stability, internality, globality and controllability for their cause, their optimism for change of the behaviour, their evaluation of the behaviour and a person showing the behaviour, their emotional response to the behaviour and their willingness to put extra effort in to helping change the behaviour. Data were analysed using correlation and regression methods. Carers working with people with challenging behaviour were more likely to evaluate the person more positively and report they would be more likely to offer extra effort in helping. A path analysis showed that helping behaviour was best predicted by optimism, which was best predicted by negative emotion which was best predicted by the attribution of controllability. We conclude that attributions and emotions reported by carers in response to challenging behaviour are consistent with Weiner's cognitive-emotional model of helping behaviour. Formulating carer behaviour using such models offers the possibility of using cognitive-behavioural methods in working with staff beliefs, emotions and behaviour in response to challenging behaviour.

Attitude of Health Personnel↗
PubMed1998

A corticotropin-releasing hormone type I receptor antagonist delays parturition in sheep.

In sheep, corticotropin-releasing hormone (CRH) can stimulate the fetal release of ACTH to produce a cortisol surge which leads to the onset of parturition. We tested the hypothesis that fetal CRH is a primary factor in the onset of parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to block the endogenous action of CRH. Pregnant ewes were cannulated at 130-135 days of gestation. Five catheters were placed into the amniotic sac, fetal femoral artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5 days' recovery, blood samples from maternal and fetal vessels were collected at the following times: a day before the start of infusion, at [-1, 0, 1, 2, 4, 8 and 24]h, on the first day of infusion, and thereafter daily throughout a 10-day infusion. Animals (n=6 per group) received infusions into a fetal vein of either a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil (Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The plasma samples were assayed for ACTH and cortisol using commercial RIA kits. Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9 days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036, unpaired Student's t-test). Fetal ACTH and cortisol did not change in the antalarmin-infused sheep after 3 days' infusion compared to significant increases in vehicle-infused sheep (P=0.004 and P = 0.016 respectively, ANOVA). These data show that CRH receptor antagonism in the fetus can delay the onset of parturition. It supports the hypothesis that hypothalamic CRH drives fetal production of ACTH and is essential for the onset of parturition triggered by a surge in fetal cortisol.

Adrenocorticotropic Hormone↗
PubMed1998

Vasodilator actions of urocortin and related peptides in the human perfused placenta in vitro.

Urocortin, is a recently isolated peptide belonging to the CRH family that binds with high affinity to the CRH2 receptor. Like CRH, urocortin causes hypotension in the rat, but its vasoactive actions have not yet been studied in the human. We have compared the vasoactive properties of urocortin, CRH, and urotensin-1 in the human fetal placental vasculature in vitro. Single placental lobules were bilaterally perfused (maternal and fetal sides, 5 mL/min each; 95% O2-5% CO2; 37 C), and changes in fetal arterial perfusion pressure were recorded. Submaximal vasoconstriction was induced by PGF2alpha (4+/-0.7 micromol/L), which increased perfusion pressure from 19.6+/-1.4 to 100.7+/-3.1 mm Hg (n=38; P < 0.001). Subsequent fetal arterial infusion of urocortin (0.001-1 nmol/L) caused concentration-dependent vasodilatation. Urocortin was equipotent with urotensin-1 and 25 times more potent than CRH in causing vasodilatation. Nevertheless, the maximum vasodilator responses to each of the peptides were similar (P > 0.05). The CRH receptor antagonist, alpha-helical CRH-(9-41) (0.2 nmol/L) significantly attenuated the vasodilatation produced by urocortin, urotensin-1, and CRH (P < 0.05). These results indicate a possible physiological role for urocortin in the modulation of human fetal placental vascular tone by activation of CRH2-like receptors.

Adolescent↗
PubMed1998

Corticotropin-releasing hormone directly and preferentially stimulates dehydroepiandrosterone sulfate secretion by human fetal adrenal cortical cells.

Estrogens produced by the placenta play a pivotal role in the endocrine control of pregnancy and induce many of the key changes involved in parturition. The placentae of humans and higher primates use the C19 androgen dehydroepiandrosterone sulfate (DHEA-S) supplied by the fetal adrenals as the principal substrate for estrogen synthesis. Thus, secretion of androgens by the fetal adrenals may be central to the process of primate parturition. The timing of human parturition also is correlated with placental CRH concentrations in the maternal circulation. Because the mechanisms that regulate DHEA-S production by the fetal adrenals are incompletely understood, we examined whether there is a functional relationship between CRH and steroid production by human fetal adrenal cortical cells. Using Northern blot analysis, we detected messenger RNA transcripts (2.7 kb) encoding the type-1 CRH receptor in total RNA extracted from midgestation human fetal adrenals, suggesting that the fetal adrenal cortex may be directly responsive to CRH. To test this, primary cultures of human fetal adrenal cortical cells were exposed to human CRH. Human CRH increased DHEA-S production by cultured human fetal adrenal cortical cells in a dose-dependent fashion, with an ED50 of 10-100 pmol/L. Human CRH was as effective as ACTH at stimulating DHEA-S production; however, it was 70% less potent than ACTH at stimulating cortisol production, indicating that its actions were preferentially directed toward increasing DHEA-S synthesis. Consistent with this thesis, we found that CRH increased abundance of messenger RNA encoding cytochrome P450 cholesterol side-chain cleavage and 17alpha-hydroxylase/17,20 lyase but not 3beta-hydroxysteroid dehydrogenase in adrenal cells. CRH did not alter cell number, indicating that it is not mitogenic for fetal adrenal cortical cells. These data demonstrate a direct functional interaction between CRH and the fetal adrenal. Therefore, placental CRH production, which rises exponentially during human pregnancy, may play a key role in promoting DHEA-S production by the fetal adrenals, which could lead to increasing placental estrogen synthesis and contribute to the process of parturition in humans.

Adrenal Cortex↗
PubMed1998

Integrated exposure uptake biokinetic model for lead in children: empirical comparisons with epidemiologic data.

The concept of model validation is evolving in the scientific community. This paper addresses the comparison of observed and predicted estimates as one component of model validation as applied to the integrated exposure uptake biokinetic (IEUBK) model for lead in children. The IEUBK model is an exposure (dose)-response model that uses children's environmental lead exposures to estimate risk of elevated blood lead (typically > 10 micrograms/dl) through estimation of lead body burdens in a mass balance framework. We used residence-specific environmental lead measurements from three epidemiologic datasets as inputs for the IEUBK model to predict blood lead levels, and compared these predictions with blood lead levels of children living at these residences. When the IEUBK modeling focused on children with representative exposure measurements, that is, children who spent the bulk of their time near the locations sampled, there was reasonably close agreement between observed and predicted blood lead distributions in the three studies considered. Geometric mean observed and predicted blood lead levels were within 0.7 microgram/dl, and proportions of study populations expected to be above 10 micrograms/dl were within 4% of those observed.

Age Factors↗
PubMed1998

Clinical and neurocognitive effects of clozapine and risperidone in treatment-refractory schizophrenic patients: a prospective study.

BACKGROUND: Few controlled studies have compared the efficacy of clozapine and risperidone in treatment-refractory schizophrenic patients. The present study investigates the efficacy of both clozapine and risperidone on psychopathologic and neurocognitive measures in a prospective 12-week open-label trial in treatment-refractory schizophrenic patients from state psychiatric hospitals. METHOD: Thirty-five DSM-IV schizophrenic patients with a documented history of nonresponse to typical neuroleptics were treated with either clozapine or risperidone. Response was assessed every 2 weeks by independent raters with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, neurologic rating scales, and plasma drug levels. Neurocognitive tests were administered at baseline and week 12. RESULTS: Both clozapine and risperidone brought about significant (p < .003) overall improvement in psychopathology. However, clozapine was numerically superior to risperidone on PANSS total scores and PANSS positive, negative, excitement, and cognitive factors. Extrapyramidal side effects were minimal for clozapine, whereas some were present for risperidone. Patients taking risperidone improved significantly in the beginning stages of the study and remained stable thereafter. Patients taking clozapine showed a gradual improvement that occurred over the entire length of the trial. Neurocognitive measures showed minimal improvement and did not differentiate between the 2 medication groups. CONCLUSION: Both clozapine and risperidone were comparably effective across a wide spectrum of psychopathologic measures. While the efficacy of clozapine was only numerically superior to that of risperidone, it was associated with fewer extrapyramidal side effects and with progressive improvement over the 12-week treatment period, suggesting that in longer trials clozapine may prove to be superior to risperidone in neuroleptic-refractory patients.

Adult↗
PubMed1998

Fibrodysplasia (myositis) ossificans progressiva. Clinical lessons from a rare disease.

Fibrodysplasia (myositis) ossificans progressiva is a rare dominantly inherited disorder, in which defects in skeletal patterning particularly affecting the big toes, are associated with progressive endochondral ossification of the large striated muscles in a specific order leading to prolonged disability. A recent series of 28 patients studied for as many as 24 years exemplifies the presentation and course of this disease. Painful swelling of muscles (myositis) leading to ossification began at a mean age of 4.6 years (range, 0-16 years) initially in the neck and upper spine (in 25 subjects) and later around the hips, other major joints, and jaw. The rate and extent of disability was unrelated to the time of onset. No form of treatment produced consistent benefit. Despite the unique clinical features, the initial diagnosis of fibrodysplasia ossificans progressiva was often wrong and usually considerably delayed. Mistaken histologic diagnoses such as soft tissue sarcoma or fibromatosis could lead to inappropriate treatment.

Adolescent↗
PubMed1998

[Contribution of chromosomal abnormalities to in vitro fertilization failures].

BACKGROUND: Present knowledge of mechanisms involved in human fertilization has uncovered a new group of pathologic conditions that have been generically named fertilization abnormalities. AIM: To determine the contribution of chromosomal alterations to in vitro fertilization failures. MATERIALS AND METHODS: A cytogenetic analysis of oocytes that were not fertilized after insemination with normal spermatozoa. Oocytes were obtained from patients subjected to in vitro fertilization in a public hospital of Metropolitan Santiago. Ovulation was induced in these patients administering GnRh-a, FSH, HMG and HCG. The double fixation technique described by Wramsby was used to obtain chromosomes. RESULTS: One hundred and seven oocytes coming from 45 women aged 25 to 42 years old were studied. The frequency of aneuploidy in these oocytes was 37.3%, with a 11.8% of hypohaploidy, a 21.6% of hyperhaploidy and a 3.9% of diploid oocytes. In hyperhaploid as well as in hypohaploid oocytes, the chromosomes involved in aneuploidy pertained to groups D. and G. CONCLUSIONS: Although the total frequency of aneuploidy is within normal ranges, the frequency of hyperhaploidy is superior to previous reports. An explanation for this finding could be that the occurrence of a lack of disjunction with chromosomal retention in the parental cell occurs with a higher frequency than that in which the chromosomes are retained in the polocyte. We also suggest that oocyte chromosomal aneuploidy could contribute to the failure of in vitro fertilization procedures.

Adult↗
PubMed1998

Partner notification and focused intervention as a means of identifying HIV-positive patients.

Partner notification as a means of contact tracing human immunodeficiency virus (HIV)-infected persons remains controversial. It is argued against by many gay activists, while primary public health officials and leaders in ethnic communities continue to support this as a means of identifying unknown cases. Human immunodeficiency virus-positive patients were interviewed to determine if partner notification could be a useful instrument. Based on interviews, patients at risk of infection through heterosexual contact were able to identify most of their sexual partners; the majority of these patients were women. Twenty-two of 22 women infected heterosexually were able to identify all of their sexual partners. Five of 8 heterosexual men were able to identify all of their sexual partners, but these men were infected through intravenous drug use. Six of 44 homosexual men interviewed were able to make these identifications. Two focus groups of homosexual men who were HIV-positive patients were organized; each was asked one question. Men in group B were asked if they could identify HIV-positive persons whom they suspected were not in a treatment program. Men in group A were asked if they they thought they knew HIV-positive persons still practicing unsafe sex. Thirteen of the 14 patients in group A were able to identify 30 persons they felt were still practicing unsafe sex; 17 of 30 tested HIV-positive and 9 were unaware of their status. The 14 patients in group B identified 15 persons they felt were HIV-positive; 11 were found to be HIV-positive and 8 were unaware of their status. These findings suggest that partner notification definitely has a role in heterosexual contact tracing, and focused intervention is a more cost-effective approach to early intervention.

Adult↗
PubMed1998

Fat embolism syndrome in a patient demonstrating only neurologic symptoms.

Fat embolism syndrome (FES) is a recognized complication of both long bone fractures and intramedullary orthopedic procedures. The usual presenting features are respiratory failure, neurologic dysfunction and petechiae. In this report, a 25-year-old woman with FES presented with serious neurologic symptoms and signs in the absence of respiratory dysfunction. The diagnosis is essentially a clinical one, but nuclear magnetic resonance imaging of the brain revealed distinctive lesions that may help future diagnosis of FES.

Adult↗
PubMed1997

17 beta-Estradiol-mediated growth inhibition of MDA-MB-468 cells stably transfected with the estrogen receptor: cell cycle effects.

Estrogen receptor (ER)-negative MDA-MB-468 human breast cancer cells were stably transfected with wild-type human ER and utilized as a model for investigating estrogen- and aryl hydrocarbon (Ah)-responsiveness. Treatment of the stably transfected cells with 10 nM 17 beta-estradiol (E2) resulted in a significant inhibition (> 60%) of cell proliferation and DNA synthesis, which was blocked by 10(-7) M ICI 182 780. Analysis by flow cytometry indicated that treatment with E2 increased the percentage of cells in G0/G1 (from 68.8 to 89.4) and decreased cells in S (from 18.4 to 3.4) and G2/M (from 12.8 to 7.2) phases of the cell cycle. The effects of E2 on the major cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors, retinoblastoma protein (RB), E2F-1, and cyclin-dependent kinase activities were also investigated in the stably transfected MDA-MB-468 cells. The results demonstrated that the growth inhibitory effects of 10(-8) M E2 in ER stably transfected MDA-MB-468 cells were associated with modulation of several factors required for cell cycle progression and DNA synthesis, including significant induction of the cyclin-dependent kinase inhibitor p21cip-1 ( > 4-fold increase after 12 h) and decreased E2F1 and PCNA protein levels. These results show that the growth-inhibitory effects of E2 in the stably transfected cells were due to multiple factors which result in growth arrest in G0/G1 and inhibition of DNA synthesis.

Antineoplastic Agents↗