Cryosurgical debulking of unresectable liver metastases for palliation of carcinoid syndrome.
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Carcinoid Tumor↗
Biomedical subjects
S Wilson
Publications and source records attributed to S Wilson.
Orphan G protein-coupled receptors: a neglected opportunity for pioneer drug discovery.
Access to DNA databases has introduced an exciting new dimension to the way biomedical research is conducted. 'Genomic research' offers tremendous opportunity for accelerating the identification of the cause of disease at the molecular level and thereby foster the discovery of more selective medicines to improve human health and longevity. The current challenge is to close the gap rapidly between gene identification and clinical development of efficacious therapeutics. In the present review, Jeffrey Stadel, Shelagh Wilson and Derk Bergsma outline the rationale and describe strategies for converting one large class of novel genes, orphan G protein-coupled receptors (GPCRs), into therapeutic targets. Historically, the superfamily of GPCRs has proven to be among the most successful drug targets and consequently these newly isolated orphan receptors have great potential for pioneer drug discovery.
Amino Acid Sequence↗
A risk-assessment model for foot and mouth disease (FMD) virus introduction through deboned beef importation.
We present a risk-assessment model to assess the risk of introduction of foot and mouth disease (FMD) virus associated with deboned beef importation. The model was developed in accordance with the risk-reduction procedures proposed by the European Community for meat importation. The risk reduction procedures include farm-level inspection, ante-mortem inspection, post-mortem inspection, chilling and deboning. The risk assessment was based on the prevalence of FMD-infected cattle in herds as well as the prevalence of infected herds in the exporting country. Computer simulations were carried out to evaluate the probability of FMD virus introduction by importing 100 tons of deboned beef in relation to FMD prevalence, number of cattle selected from each herd, and sample sizes in ante-mortem and post-mortem inspections. The effects of the risk-reduction procedures on the probability of FMD virus introduction were examined.
Animals↗
Genital pain associated with genital retraction: a case of Koro syndrome.
Koro is a unique psychiatric disorder in which acute anxiety accompanies the perception of genital retraction. This case report describes a case of Koro syndrome associated with penile and scrotal pain. A review of the literature has not shown any previous report of Koro associated with genital pain.
Adult↗
Stress-activated protein kinases: activation, regulation and function.
The response of cells to extracellular stimuli is mediated in part by a number of intracellular kinase and phosphatase enzymes. Within this area of research the activation of the p42 and p44 isoforms of mitogen-activated protein (MAP) kinases have been extensively described and characterised as central components of the signal transduction pathways stimulated by both growth factors and G-protein-coupled receptor agonists. Signaling events mediated by these kinases are fundamental to cellular functions such as proliferation and differentiation. More recently, homologues of the p42 and p44 isoforms of MAP kinase have been described, namely the stress-activated protein kinases (SAPKs) or alternatively the c-jun N-terminal kinases (JNKs) and p38 MAP kinase (the mammalian homologue of yeast HOG1). These MAP kinase homologues are integral components of parallel MAP kinase cascades activated in response to a number of cellular stresses including inflammatory cytokines (e.g., Interleukin-1 (Il-1) and tumour necrosis factor-alpha (TNF-alpha), heat and chemical shock, bacterial endotoxin and ischaemia/cellular ATP depletion. Activation of these MAP kinase homologues mediates the transduction of extracellular signals to the nucleus and are pivotal events in the regulation of the transcription events that determine functional outcome in response to such stresses. In this review we highlight the identification and characterisation of the stress-activated MAP kinase homologues, their role as components of parallel MAP kinase pathways and the regulation of cellular responses following exposure to cellular stress.
Animals↗
A three-step method of self-reflection using reflective journal writing.
Fiscal and financial constraints present a challenge for nurse educators to broaden the diversity and scope of teaching/learning methodologies. One method designed to promote autonomy and self-direction of nursing students is self-reflection combined with reflective journal writing. This paper describes a three-step process of self-reflection encompassing critical appraisal, peer group discussion and self-awareness. This process of self-reflection was initiated with one group of clinical nursing students. Using student and teacher feedback, implications for employing this teaching/learning strategy in clinical practice are suggested.
Education, Nursing↗
A systematic review of the psychiatric/mental health nursing research literature 1982-1992.
The purpose of this study was to assess the quality of quantitative psychiatric/mental health nursing research articles published in English between 1982 and 1992, worldwide. Criteria for selection of articles included nurse authorship or co-authorship, use of a quantitative design and pertinence to an aspect of the nursing process with psychiatric/mental health patients. One hundred and ninety-four articles met these criteria. The quality of each article was assessed by two nurse experts using Duffy's Research Appraisal Checklist (RAC). Forty-six point nine per cent of the articles were rated as superior, 50% as average and 3.1% as below average. Other findings identified journals that published research articles, countries in which research was completed, applicability of funding and qualifications of the authors. The major implications of this study are that nurses can be directed to superior articles; more publication of research by nurse authors is warranted, research is being completed with little financial support, highly rated research publications tend to get funding and editorial policies affect the quality of publication.
Authorship↗
Identity, genealogy, and the social family: the case of donor insemination.
In this paper I discuss whether or not biographical information concerning the sperm donor should be disclosed to children conceived through donor insemination. Policies of disclosure for example in the context of adoption, have been justified on the basis of a notion of identity which emphasizes genetic ties. This notion of identity and the policies of disclosure of information concerning biological parents based on it, have been criticized by many writers, including feminists, as reinforcing explanations of human organization and development based on biological determinism rather than on ideas such as social construction. Further, this notion of identity is seen to emphasize the importance of genetic parenthood over the commitment involved in bringing up a child as a social parent. While agreeing with these criticisms of that particular notion of identity, I argue that the notion of identity as a whole should not be summarily rejected. Rather, it should be re-interpreted using a sociological approach incorporating the notion of narrative. This second narrative notion of identity is developed with reference to the situation of some groups of children, who like those born from donor insemination, generally do not have any knowledge of their biological parent[s], for example adoptees, the children of the disappeared in Argentina and child migrants. In this paper, policies of disclosure which allow these children to gain some knowledge of their biological parents are discussed in light of the two notions of identity. It is argued that disclosure may be justified on the basis of a narrative notion of identity. This allows for the rigid dichotomy created between biological determinism and social construction: the importance of social parents to the child is emphasized, however the desire a child may have to know something about her or his biological parent is not denied or dismissed.
Adoption↗
Analysis of dynamic radioligand displacement or "activation" studies.
We present a simple way of assessing dynamic or time-dependent changes in displacement during single-subject radioligand positron emission tomography (PET) activation studies. The approach is designed to facilitate dynamic activation studies using selective radioligands. These studies are, in principle, capable of characterising functional neurochemistry by analogy with the study of functional neuroanatomy using rCBF activation studies. The proposed approach combines time-dependent compartmental models of tracer kinetics and the general linear model used in statistical parametric mapping. This provides for a comprehensive, voxel-based and data-led assessment of regionally specific effects. The statistical model proposed in this paper is predicated on a single-compartment model extended to allow for time-dependent changes in kinetics. We have addressed the sensitivity and specificity of the analysis, as it would be used operationally, by applying the analysis to 11C-Flumazenil dynamic displacement studies. The activation used in this demonstration study was a pharmacological (i.v. midazolam) challenge, 30 min after administration of the tracer. We were able to demonstrate, and make statistical inferences about, regional increases in k2 (or decreases in the volume of distribution) in prefrontal and other cortical areas.
Activation Analysis↗
Epidemiology of dental trauma treated in an urban pediatric emergency department.
STUDY OBJECTIVE: To describe the epidemiology of traumatic dental injuries to children treated in an urban pediatric emergency department (ED). DESIGN: A descriptive study of a consecutive series of patients. SETTING: The ED of a large, academic children's hospital. PARTICIPANTS: Children presenting to the ED with dental trauma from December 1992 to November 1993. RESULTS: Of 1459 children treated for dental emergencies, 541 had dental trauma (37%) and were enrolled in this study. Patients ranged in age from five months to 18 years. Fifty-nine percent of patients were less than seven years of age, and 59% of patients were male. Falls caused 63% of injuries, followed by being struck (17%), and motor vehicle crashes (2%). Injuries to the soft tissues included lacerations (32%), swelling (8%), abrasions (7%), and contusions (6%). Injuries to hard dental structures included tooth fractures (33%), luxations (18%), concussions (12%), avulsions (8%), and jaw fractures (1%). Tooth luxation and concussion were more common among children less than seven years of age, and fractures to the tooth crown with dentin exposure (Ellis class II) were seen most often among children with permanent dentition (chi 2 = 41.4, P < 0.005). The central incisors were the teeth most frequently traumatized. CONCLUSION: Findings of this large consecutive series provide a useful description of the epidemiology of this common type of pediatric trauma for pediatric emergency care providers.
Accidental Falls↗
Characterization of the influence of some cyclodextrins on the stratum corneum from the hairless mouse.
Differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) have been used to determine the influence of beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-CyD (HP-beta-CyD) and gamma-CyD on the structural properties of the stratum corneum from the hairless mouse. Some modest changes in the stratum corneum lipid transition temperature were induced by HP-beta-CyD and blue shifts were observed in the FTIR spectra of the C-H asymmetric and symmetric stretching of the lipids from the stratum corneum. Results from TEM studies indicated that HP-beta-CyD caused removal and possible disorganization of the lipid matrix that envelopes the corneocytes of the stratum corneum, whereas no effect was seen after treatment of the samples with beta-CyD and gamma-CyD. These results suggest that HP-beta-CyD can increase the permeability of the stratum corneum possibly as a result of extraction of lipids, and might thus enhance drug permeation through the skin.
2-Hydroxypropyl-beta-cyclodextrin↗
Obstacles to research in A&E.
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Emergency Medicine↗
Effects of high dose intravenous immunoglobulin in two severe corticosteroid insensitive asthmatic patients.
Preliminary observations of the clinical efficacy of intravenous immunoglobulin in two patients with severe corticosteroid insensitive asthma are reported. In both patients treatment with intravenous immunoglobulin resulted in clinical improvement and enabled a significant reduction in the dose of prednisolone. In one of the patients fibreoptic bronchoscopy with endobronchial biopsies was performed and peripheral blood was analysed by flow cytometry before and after treatment. Immunohistological analysis of the biopsy samples after treatment showed a decrease in the number of all cell types, especially CD3+ T cells, CD4+ T cells, and activated CD25+ T lymphocytes, which was associated with a reduction in peripheral blood T cell activation. Intravenous immunoglobulin may be a valid option for the treatment of corticosteroid insensitive asthma. To elucidate the role and mode of action of intravenous immunoglobulin further studies in larger groups of patients are needed.
Adolescent↗
Nontraumatic dental emergencies in a pediatric emergency department.
The objectives of this study were to describe nontraumatic dental emergencies among children treated in a pediatric emergency department. The children studied received emergency treatment for a nontraumatic dental problem from December 1992 through November 1993. Among the 1,459 children treated for dental emergencies, 949 had a nontraumatic emergency (65%) and were enrolled in this study. Patients ranged in age from 1 month to 19 years, with a mean age of 6.9 years. Fifty-two percent of patients were male. The teeth were involved in 99% of cases. An abscess was present in 33% of patients; and among these patients, 26% also had a fistula. Pericoronitis was seen in 4% of patients, primary viral stomatitis in 1%, and an eruption hematoma in 0.5%. Caries is the etiology of the problem prompting the emergency department visit in 73% of patients, and baby bottle caries accounted for 18% of all cases of caries. Other etiologies included the late effects of trauma (8%), iatrogenic (7%), idiopathic (3%), and periodontal processes (2%). Tooth extraction was performed in 45% of patients. Findings of this large consecutive series provide a better understanding of this type of visit to the pediatric emergency department.
Adolescent↗
Antidepressant drugs and the cardiovascular system: a comparison of tricylics and selective serotonin reuptake inhibitors and their relevance for the treatment of psychiatric patients with cardiovascular problems.
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Antidepressive Agents, Tricyclic↗
Ethnic variation in the incidence of HELLP syndrome in a hypertensive pregnant population.
To determine whether there is a difference among various ethnic groups in the complication of HELLP syndrome in a hypertensive pregnant population. A cohort of 498 pregnant women were entered into the study and multiple clinical parameters including blood pressure, birthweight percentile, gestational age were abstracted. HELLP syndrome was diagnosed in patients based on thrombocytopenia elevated liver enzymes and hemolysis. Maternal and fetal characteristics including the incidence of HELLP syndrome were compared among various ethnic groups and between the hypertensive categories using analysis of variance. The risk of developing HELLP syndrome was significantly higher in the White and Chinese population compared to the East Indian population (relative risk of 2.2). The development of HELLP syndrome was associated with an increased risk of the development of small for gestational age infants (SGA). The clinical correlates of the HELLP syndrome include ethnic group being highest in Chinese and White populations. A significant risk for the development of small for gestational age infants (SGA) exists in the presence of the HELLP syndrome.
British Columbia↗
Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat.
Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.
Adipose Tissue, Brown↗
Immunotoxicity of 2',3'-dideoxyinosine in female B6C3F1 mice.
2',3'-dideoxyinosine (ddI) is one of several purine analogues used for the treatment of HIV and the acquired immunodeficiency syndrome (AIDS). These nucleoside analogues are promising in their inhibition of viral reverse transcriptase and termination of DNA synthesis. However, each of these drugs has toxicity associated with its use. A previous immunotoxicological evaluation of 2',3'-dideoxyadenosine (ddA), the parent compound of ddI, showed that ddA suppresses humoral immunity. These studies were undertaken to determine the potential for immunotoxicity due to treatment with ddI. This evaluation included an assessment of innate and acquired immunity after exposure to ddI (100, 250, 500, and 1000 mg/kg/day) for 14, 28 or 180 days. There were no overt signs of toxicity related to treatment with ddI except for a decrease in body weight in the group treated with the highest dose of ddI for 180 days. Overall, 6 months of treatment with ddI showed minimal effects on specific organs with the exception of the spleen and thymus. ddI selectively targets the immune system, with assays that challenge humoral immunity being more affected than those testing cell-mediated immunity. Innate immunity was unaffected by ddI treatment. Cell-mediated immunity, as measured by proliferative response to allogeneic cells (MLR) and the T cell mitogen (Concanavalin A), was moderately suppressed. There were no ddI associated effects on NK function or macrophage function as measured by the vascular clearance rate and phagocytic uptake of the tissue macrophages. The most sensitive indicator of ddI-induced immunotoxicity is suppression of the response to the T-dependent antigen, sheep red blood cells (sRBC). The No Observable Adverse Effect Level (NOAEL) for toxicity to the immune system following 14 days of exposure to ddI is 250 mg/kg. A suppression of the humoral immune response was seen at the lowest dose tested after treatment for 28 and 180 days. Thus, the NOAEL for both of these treatment periods is below 100 mg/kg/day.
Animals↗