RÉSUMÉ
WHAT IS KNOWN ON THE SUBJECT?: The concept of compassion is well documented in the healthcare literature but has received limited attention in mental health nursing. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Mental health nurses struggle with defining compassion. The study, with its limitations, brings greater clarity to the meaning of compassion for community mental health nurses and NHS organizations. Mental health nurses need time to reflect on their provision of compassionate care. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The study has shown that compassion is important for NHS healthcare management, frontline mental health nurses and policy-makers in UK, and there is potential for sharing practice and vision across NHS organisations. Mental health nurses could benefit from training to facilitate their understanding of compassionate practices. Emphasis should be placed on the importance of self-compassion and how this can be nurtured from the secure base of clinical supervision. ABSTRACT: Introduction There is increasing emphasis in policy, research and practice in the UK and internationally on the importance of caring in health care. Compassion needs to be at the core of all healthcare professionals' practice. Recently, health care has received negative attention through media and government reports which cite a lack of compassion in care. Rationale The concept of compassion has received limited attention in community mental health nursing. Aim Based on data taken from semi-structured interviews with community mental health nurses, this paper aims to describe interpretations and perspectives of compassion to gain insight and development of its meaning. Method A naturalistic, interpretive approach was taken to the study. Semi-structured interviews with nine mental health nurses were analysed using Burnard's 14-step model of thematic analysis. Findings The research illuminates the complexity of compassion and how its practice impacts on emotional responses and relationships with self, patients, colleagues and the employing organization. Participants identified difficulties engaging with compassionate practice whilst recognizing it as a driving force underpinning provision of care. Implications for practice Mental health nurses need to be supported to work towards a greater understanding of compassionate care for clinical practice and the need for self-compassion.
Sujet(s)
Attitude du personnel soignant , Services communautaires en santé mentale , Empathie , Infirmières en santé communautaire/psychologie , Soins infirmiers en psychiatrie , Adulte , Femelle , Humains , Mâle , Recherche qualitativeRÉSUMÉ
OBJECTIVES: Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin's B-box domain is necessary for interactions with proline serine threonine phosphatase interacting protein 1 (PSTPIP1). The aim was to characterise the phenotype of patients with these substitutions and to determine their functional significance. METHODS: A database of genetic tests undertaken at the US National Institutes of Health was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Coimmunoprecipitation techniques were employed to determine the variants' effects on pyrin/PSTPIP1 interactions. RESULTS: A total of 40 symptomatic and 4 asymptomatic family members with these substitutions were identified. P369S and R408Q were found in cis, and cosegregated in all patients sequenced. Clinical details were available on 22 patients. In all, 5 patients had symptoms and signs fulfilling a clinical diagnosis of FMF, and 15 received colchicine. In patients not achieving the criteria, trials of anti-tumour necrosis factor (TNF) agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Coimmunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. CONCLUSIONS: P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modelling studies suggest that these substitutions do not significantly affect pyrin's interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms.
Sujet(s)
Protéines du cytosquelette/génétique , Fièvre méditerranéenne familiale/génétique , Mutation , Adolescent , Adulte , Âge de début , Enfant , Enfant d'âge préscolaire , Colchicine/usage thérapeutique , Fièvre méditerranéenne familiale/diagnostic , Fièvre méditerranéenne familiale/traitement médicamenteux , Prédisposition génétique à une maladie , Génotype , Humains , Nourrisson , Antagoniste du récepteur à l'interleukine-1/usage thérapeutique , Adulte d'âge moyen , Pyrine , Études rétrospectives , Résultat thérapeutique , Facteur de nécrose tumorale alpha/antagonistes et inhibiteurs , Jeune adulteRÉSUMÉ
BACKGROUND: There has been a lack of appropriate classification criteria for vasculitis in children. OBJECTIVE: To develop a widely accepted general classification for the vasculitides observed in children and specific and realistic classification criteria for common childhood vasculitides (Henoch-Schönlein purpura (HSP), Kawasaki disease (KD), childhood polyarteritis nodosa (PAN), Wegener's granulomatosis (WG), and Takayasu arteritis (TA)). METHODS: The project was divided into two phases: (1) the Delphi technique was used to gather opinions from a wide spectrum of paediatric rheumatologists and nephrologists; (2) a consensus conference using nominal group technique was held. Ten international experts, all paediatricians, met for the consensus conference. Agreement of at least 80% of the participants was defined as consensus. RESULTS: Consensus was reached to base the general working classification for childhood vasculitides on vessel size. The small vessel disease was further subcategorised into "granulomatous" and "non-granulomatous." Final criteria were developed to classify a child as HSP, KD, childhood PAN, WG, or TA, with changes introduced based on paediatric experience. Mandatory criteria were suggested for all diseases except WG. CONCLUSIONS: It is hoped that the suggested criteria will be widely accepted around the world because of the reliable techniques used and the international and multispecialist composition of the expert group involved.
Sujet(s)
Vascularite/classification , Enfant , Syndrome de Churg-Strauss/classification , Méthode Delphi , Granulomatose avec polyangéite/classification , Humains , /classification , Coopération internationale , Maladie de Kawasaki/classification , Polyartérite noueuse/classification , Maladie de Takayashu/classificationRÉSUMÉ
The National Institute of Allergy and Infectious Disease, National Institutes of Health, convened a workshop entitled The Next Step: Protocol Development for Autologous Stem Cell Transplantation for Pediatric Rheumatic Disease, June 2000, co-chaired by Drs. Karyl Barron and Carol Wallace. The goal of the workshop was to focus on the scientific rationale for stem cell transplantation therapy in the pediatric diseases, unique aspects of this therapy in the pediatric rheumatic diseases, transplantation issues and options, regulatory issues, and development of a DNA repository for these diseases.
Sujet(s)
Transplantation de cellules souches hématopoïétiques/méthodes , Transplantation de cellules souches hématopoïétiques/normes , Rhumatismes/thérapie , Enfant , Humains , Transplantation autologueRÉSUMÉ
Currently, there is a debate about which types of achievement goals promote optimal motivation. A number of theorists argue for a mastery goal perspective focusing on the adaptive consequences of mastery goals and the maladaptive consequences of performance goals. Others endorse a multiple goal perspective in which both mastery and performance goals can be beneficial. The purpose of the present investigation was to review why this debate has emerged and to offer a critical test of the mastery versus multiple goal perspectives. In Study 1, a correlational approach was used to identify the optimal goals for college participants to adopt for a learning activity. In Study 2, an experimental approach was used to identify the optimal goals to assign for the same activity. Each study revealed benefits of both mastery and performance goals, providing support for the multiple goal perspective.
Sujet(s)
Accomplissement , Objectifs , Motivation , Résolution de problème , Adulte , Femelle , Humains , Apprentissage , Mâle , Modèles psychologiques , Plan de rechercheRÉSUMÉ
This study examined whether spinal cord stimulation (SCS) at intensities below motor threshold (MT) produces cutaneous vasodilation through sympathetic inhibition and/or antidromic activation of sensory fibers. SCS was applied to anesthetized rats with stimulus parameters used clinically, i.e. 50 Hz, 0.2 ms and stimulus intensities at 30, 60 or 90% of MT. SCS-induced vasodilation was not attenuated by hexamethonium, an autonomic ganglion blocking agent, but was abolished by CGRP-(8-37), an antagonist of the calcitonin gene-related peptide (CGRP) receptor. We concluded that SCS-induced vasodilation under the conditions of this study was mediated by peripheral release of CGRP via antidromic activation of sensory fibers.
Sujet(s)
Peptide relié au gène de la calcitonine/métabolisme , Fragments peptidiques/métabolisme , Peau/vascularisation , Moelle spinale/physiologie , Vasodilatation/physiologie , Animaux , Pression sanguine/physiologie , Peptide relié au gène de la calcitonine/pharmacologie , Stimulation électrique , Ganglioplégiques/pharmacologie , Rythme cardiaque/physiologie , Hexaméthonium/pharmacologie , Mâle , Neurones afférents/métabolisme , Fragments peptidiques/pharmacologie , Rats , Rat Sprague-Dawley , Système nerveux sympathique/physiologie , Vasodilatation/effets des médicaments et des substances chimiquesRÉSUMÉ
OBJECTIVE: We report 16 infants with complete congenital heart block (CHB) who developed late-onset dilated cardiomyopathy despite early institution of cardiac pacing. BACKGROUND: Isolated CHB has an excellent prognosis following pacemaker implantation. Most early deaths result from delayed initiation of pacing therapy or hemodynamic abnormalities associated with congenital heart defects. METHODS: A multi-institutional study was performed to identify common clinical features and possible risk factors associated with late-onset dilated cardiomyopathy in patients born with congenital CHB. RESULTS: Congenital heart block was diagnosed in utero in 12 patients and at birth in four patients. Ten of 16 patients had serologic findings consistent with neonatal lupus syndrome (NLS). A pericardial effusion was evident on fetal ultrasound in six patients. In utero determination of left ventricular (LV) function was normal in all. Following birth, one infant exhibited a rash consistent with NLS and two had elevated hepatic transaminases and transient thrombocytopenia. In the early postnatal period, LV function was normal in 15 patients (shortening fraction [SF] = 34 +/- 7%) and was decreased in one (SF = 20%). A cardiac pacemaker was implanted during the first two weeks of life in 15 patients and at seven months in one patient. Left ventricular function significantly decreased during follow-up (14 days to 9.3 years, SF = 9% +/- 5%). Twelve of 16 patients developed congestive heart failure before age 24 months. Myocardial biopsy revealed hypertrophy in 11 patients, interstitial fibrosis in 11 patients, and myocyte degeneration in two patients. Clinical status during follow-up was guarded: four patients died from congestive heart failure; seven required cardiac transplantation; one was awaiting cardiac transplantation; and four exhibited recovery of SF (31 +/- 2%). CONCLUSIONS: Despite early institution of cardiac pacing, some infants with CHB develop LV cardiomyopathy. Patients with CHB require close follow-up not only of their cardiac rate and rhythm, but also ventricular function.
Sujet(s)
Cardiomyopathie dilatée/étiologie , Bloc cardiaque/congénital , Enfant , Enfant d'âge préscolaire , Femelle , Études de suivi , Âge gestationnel , Bloc cardiaque/complications , Bloc cardiaque/diagnostic , Bloc cardiaque/thérapie , Humains , Nourrisson , Nouveau-né , Mâle , Pacemaker , Grossesse , Diagnostic prénatal , Facteurs de risqueRÉSUMÉ
The purpose of this article is to review the problems and processes impacting the deviation in first-case actual start times when compared to first-case scheduled start times. This article will also discuss the Continuous Outcomes Measurement and Improvement Technique (COMIT) model for problem resolution and share the experiences encountered by a group of collaborative nurse manager leaders in their outcome improvement efforts. The overall process improvements are discussed using the eight-step COMIT model, which showed the overall success of the project.
Sujet(s)
Modèles de soins infirmiers , Procédures orthopédiques/normes , Évaluation des résultats et des processus en soins de santé/organisation et administration , Soins périopératoires/organisation et administration , Management par la qualité/organisation et administration , Analyse de variance , Prise en charge personnalisée du patient/organisation et administration , Communication , Comportement coopératif , Efficacité fonctionnement , Hôpitaux religieux , Humains , Relations interprofessionnelles , Infirmières administratives/organisation et administration , Infirmières administratives/psychologie , Recherche en évaluation des soins infirmiers/organisation et administration , Administration des services infirmiers/organisation et administration , Soins infirmiers au bloc opératoire/organisation et administration , Soins infirmiers en orthopédie/organisation et administration , Procédures orthopédiques/soins infirmiers , Équipe soignante/organisation et administration , Soins périopératoires/soins infirmiers , Techniques de planification , Résolution de problème , Comités du personnel de santé/organisation et administration , Texas , Gestion du temps/organisation et administrationRÉSUMÉ
OBJECTIVE: Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with severe angina pectoris refractory to conventional therapeutic strategies. Clinical studies show that spinal cord stimulation (SCS) is a safe adjunct therapy for cardiac patients, producing anti-anginal as well as anti-ischemic effects. However, little information is yet available about the underlying mechanisms involved. METHODS: In order to determine its mechanism of action, the effects of SCS on the final common integrator of cardiac function, the intrinsic cardiac nervous system, was studied during basal states as well as during transient (2 min) myocardial ischemia. Activity generated by intrinsic cardiac neurons was recorded in 9 anesthetized dogs in the absence and presence of myocardial ischemia before, during and after stimulating the dorsal T1-T2 segments of the spinal cord at 66 and 90% of motor threshold using epidural bipolar electrodes (50 Hz; 0.2 ms; parameters within the therapeutic range used in humans). RESULTS: The SCS suppressed activity generated by intrinsic cardiac neurons. No concomitant change in monitored cardiovascular indices was detected. Neuronal activity increased during transient ventricular ischemia (46%), as well as during the early reperfusion period (68% compared to control). Despite that, activity was suppressed during both states by SCS. CONCLUSIONS: SCS modifies the capacity of intrinsic cardiac neurons to generate activity. SCS also acts to suppress the excitatory effects that local myocardial ischemia exerts on such neurons. Since no significant changes in monitored cardiovascular indices were observed during SCS, it is concluded that modulation of the intrinsic cardiac nervous system might contribute to the therapeutic effects of SCS in patients with angina pectoris.
Sujet(s)
Angine de poitrine/thérapie , Système nerveux autonome , Électrothérapie , Coeur/innervation , Ischémie myocardique/physiopathologie , Potentiels d'action , Animaux , Chiens , Mâle , Ischémie myocardique/thérapie , Neurones/physiologie , Répartition aléatoire , Traitement du signal assisté par ordinateur , Moelle spinaleRÉSUMÉ
The present study examined the effects of stereotaxic delivery of corticosterone to the amygdala on anxiety-like behavior and corticotropin-releasing factor (CRF) mRNA level in the central nucleus of the amygdala (CeA). Micropellets (30 microg) of crystalline corticosterone or cholesterol (control) were implanted bilaterally at the dorsal margin of the CeA in Wistar rats. Seven days post-implantation, anxiety-like behavior was accessed using an elevated plus-maze. CRF mRNA level in the CeA was determined by in situ hybridization 4 h after being tested on the elevated plus-maze. Corticosterone implants increased indices of anxiety on the elevated plus-maze and produced a concomitant increase in both basal level of CRF mRNA per neuron and the number of neurons with CRF hybridization signal in the CeA. The plus-maze increased CRF mRNA levels in the CeA of cholesterol implanted rats to the elevated basal levels observed in corticosterone treated animals. Exposure to the plus-maze did not increase CRF mRNA level in the CeA of corticosterone implanted rats beyond elevated basal levels. Taken together, these findings support the involvement of the amygdala in anxiety-like behaviors in response to chronically elevated corticosterone and suggests that elevated glucocorticoids may increase anxiety by inducing CRF expression in the CeA.
Sujet(s)
Amygdale (système limbique)/effets des médicaments et des substances chimiques , Anti-inflammatoires/pharmacologie , Corticostérone/pharmacologie , Corticolibérine/effets des médicaments et des substances chimiques , Activité motrice/effets des médicaments et des substances chimiques , Amygdale (système limbique)/métabolisme , Animaux , Anxiété/métabolisme , Cholestérol/pharmacologie , Corticolibérine/métabolisme , Mâle , Activité motrice/physiologie , ARN messager/effets des médicaments et des substances chimiques , ARN messager/métabolisme , Rats , Rat WistarRÉSUMÉ
The purpose of this study was to determine the involvement of supraspinal centers and spinal synaptic integration in cutaneous vasodilation mediated by dorsal spinal cord stimulation (DCS). Laser Doppler flowmetry was used to assess cutaneous blood flow changes in the rat hindpaw during DCS with a unipolar ball electrode placed at the L2-L3 spinal level. Results demonstrated that transecting the spinal cord at the T10 spinal segment did not alter the DCS response while T13 spinal transection abolished the DCS-induced vasodilation. Inhibition of synaptic activity with topical application of muscimol (0.2 mM) on the dorsal surface of the spinal cord markedly attenuated the DCS response. In conclusion DCS-induced vasodilation involved synaptic integration but did not require input from rostral spinal sites or supraspinal areas.
Sujet(s)
Peau/vascularisation , Moelle spinale/physiologie , Vasodilatation/physiologie , Animaux , Cordotomie , Stimulation électrique , Agonistes GABA/pharmacologie , Fluxmétrie laser Doppler , Mâle , Microcirculation/effets des médicaments et des substances chimiques , Muscimol/pharmacologie , Rats , Rat Sprague-Dawley , Débit sanguin régional/effets des médicaments et des substances chimiques , Débit sanguin régional/physiologie , Peau/effets des médicaments et des substances chimiques , Moelle spinale/effets des médicaments et des substances chimiques , Racines des nerfs spinaux/effets des médicaments et des substances chimiques , Racines des nerfs spinaux/physiologie , Synapses/effets des médicaments et des substances chimiques , Synapses/physiologie , Vasodilatation/effets des médicaments et des substances chimiquesRÉSUMÉ
The National Institute of Allergy and Infectious Disease, National Institutes of Health convened a workshop on Kawasaki disease, May 1997, co-chaired by Drs. Karyl Barron and Stanford Shulman. The goal of the workshop was to review the latest scientific advances relating to the epidemiology, etiology, pathogenesis, treatment, and complications of Kawasaki disease, along with future therapeutic options and proposed future research directions.
Sujet(s)
Maladie de Kawasaki , Maladie coronarienne/étiologie , Éducation , Prévision , Humains , Maladie de Kawasaki/complications , Maladie de Kawasaki/épidémiologie , Maladie de Kawasaki/physiopathologie , Maladie de Kawasaki/thérapie , National Institutes of Health (USA) , États-Unis , Vascularite/étiologieRÉSUMÉ
OBJECTIVE: To determine the efficacy of a daily cyclophosphamide (CYC) and glucocorticoid induction and methotrexate (MTX) remission-maintenance regimen for the treatment of Wegener's granulomatosis (WG). METHODS: An open-label, prospective, standardized trial for the treatment of WG was performed using CYC and glucocorticoids for remission induction and MTX for remission maintenance. Thirty-one patients were enrolled in this study. Outcome was assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. RESULTS: The use of CYC and glucocorticoids for remission induction and MTX for remission maintenance resulted in disease remission for all 31 patients. The median time to remission was 3 months and the median time to discontinuation of glucocorticoids was 8 months. No patients have died, and 5 patients (16%) have had disease relapses at a median of 13 months after achieving remission. Only 2 patients (6%) have had to withdraw from the trial as a result of medication toxicity. CONCLUSION: The use of CYC and glucocorticoids for remission induction and MTX for remission maintenance was shown by this study to be an acceptable alternative therapy for patients with active WG, including those with severe disease at onset.
Sujet(s)
Granulomatose avec polyangéite/thérapie , Adolescent , Adulte , Sujet âgé , Enfant , Cyclophosphamide/administration et posologie , Femelle , Glucocorticoïdes/pharmacologie , Humains , Mâle , Méthotrexate/pharmacologie , Adulte d'âge moyen , Induction de rémission , Prévention secondaireRÉSUMÉ
Vagal motor outflow from the dorsal vagal complex is important in the regulation of intestinal motility. The aim of our study was to test the hypothesis that within the dorsal vagal complex, tonic GABA(A)-receptor mediated neurotransmission modulates intestinal motility. The GABA(A) receptor antagonist, bicuculline (methiodide), was microinjected into the dorsal vagal complex, and the effects on small intestinal and colonic motility were investigated. Rats were anesthetized and the mean arterial pressure and heart rate were monitored. Jejunal and colonic motility were measured manometrically, and motility indices were calculated manually. Bicuculline at concentrations of 0.25 or 0.5 mM in 30 nl was microinjected bilaterally into the dorsal vagal complex through stereotaxically placed micropipettes. The injection sites were confirmed histologically using the dye Alcian Blue. Bicuculline (0.5 mM) inhibited spontaneous jejunal motility by 76.3%, colonic motility by 51.7%, mean arterial pressure by 23.3% and heart rate by 27.6%. The lower concentration of bicuculline (0.25 mM) showed no inhibitory effects on intestinal motility but decreased mean arterial blood pressure by 24.1% and heart rate by 13.6%. Bilateral cervical vagotomy attenuated the bicuculline (0.5 mM)-induced inhibition of spontaneous jejunal motility, whereas the bicuculline effect on colonic motility was unaffected. The results of this study show that GABA(A) receptor-mediated neurotransmission in the dorsal vagal complex is involved in autonomic integration of motility of the small intestine and colon. Furthermore, our results indicate that the dorsal vagal complex regulation of jejunal motility involves vagal outflow, whereas vagal pathways do not participate in the bicuculline-induced inhibition of colonic motility.
Sujet(s)
Bicuculline/pharmacologie , Antagonistes GABA/pharmacologie , Antagonistes du récepteur GABA-A , Moelle allongée/physiologie , Transmission synaptique/physiologie , Nerf vague/physiologie , Animaux , Côlon/effets des médicaments et des substances chimiques , Côlon/innervation , Côlon/physiologie , Motilité gastrointestinale/effets des médicaments et des substances chimiques , Motilité gastrointestinale/physiologie , Techniques in vitro , Jéjunum/effets des médicaments et des substances chimiques , Jéjunum/innervation , Jéjunum/physiologie , Mâle , Moelle allongée/effets des médicaments et des substances chimiques , Microinjections , Rats , Rat Sprague-Dawley , Transmission synaptique/effets des médicaments et des substances chimiques , Vagotomie , Nerf vague/effets des médicaments et des substances chimiquesRÉSUMÉ
Kawasaki disease is an acute systemic vasculitis of childhood. Children are predominantly affected at less than 5 years of age, and coronary artery involvement is responsible for most of the morbidity and mortality of the disease. Since the institution of intravenous immune globulin in the treatment of the disease, outcome has significantly improved. Although multiple infectious agents and toxins have been implicated in the etiology of the disease, none has been identified. Activation of the immune system is known to occur in the acute stage of the disease and plays an important role in the pathogenesis of the disease.
Sujet(s)
Maladie de Kawasaki/immunologie , Maladies cardiovasculaires/complications , Enfant , Enfant d'âge préscolaire , Humains , Japon/épidémiologie , Maladie de Kawasaki/épidémiologie , Maladie de Kawasaki/anatomopathologie , États-Unis/épidémiologie , Vascularite/étiologie , Vascularite/immunologie , Vascularite/anatomopathologieRÉSUMÉ
Objective. In addition to treatment of refractory chronic pain in patients with peripheral vascular disease, dorsal spinal cord stimulation (DCS) increases cutaneous blood flow to the extremities and may have a limb-saving effect. The purpose of this study was to examine the role of the sympathetic nervous system in the cutaneous vasodilation due to DCS. Methods. Male Sprague-Dawley rats were anesthetized with pentobarbital (60 mg/kg, i.p.). A unipolar ball electrode was placed on the left side of the exposed spinal cord at approximately the L1-L2 level. Blood flow was concurrently recorded from both hindpaw foot pads with laser Doppler flowmeters. Blood flow responses were assessed during 1 min of DCS (0.6 mA at 50 Hz, 0.2 msec pulse duration) at 10 min intervals. To determine the contribution of the sympathetic nervous system in the blood flow response to DCS, the role of ganglionic transmission, alpha-adrenergic receptors, beta-adrenergic receptors, and adrenal catecholamine secretion were investigated using adrenergic receptor antagonists. Results. Hexamethonium (10 mg/kg, i.v.), an autonomic ganglionic receptor antagonist, did not attenuate the cutaneous vasodilation during DCS. Phentolamine (3 mg/kg, i.v.), a nonselective alpha-adrenergic receptor antagonist, also did not attenuate the DCS-induced increase in peripheral cutaneous blood flow. On the other hand, prazosin (0.1 mg/kg, i.v.), a selective alpha-1-adrenergic receptor antagonist, attenuated the DCS response but this may, at least, be partly due to a vehicle effect. Propranolol (5 mg/kg, i.v.), a nonselective beta-adrenergic receptor antagonist, attenuated the DCS response while adrenal demedullation did not. Conclusion. Overall, our results show that DCS-induced vasodilation can occur through mechanisms that are independent of sympathetic outflow.
RÉSUMÉ
The present study employed neuropharmacological and receptor binding protocols to determine if diazepam-sensitive (DS) gamma-aminobutyric acid-A (GABA(A)) receptors in the nucleus tractus solitarius (NTS) participate in autonomic regulation of cardiovascular function. The first set of protocols was designed to determine if GABA(A) receptors in the NTS were functionally modulated by the benzodiazepine agonist, diazepam. Mean arterial pressure and heart rate responses to microinjection of GABAergic substances into the NTS were examined in urethane-anesthetized rats. Microinjection of the GABA(A) agonist isoguvacine into the NTS increased mean arterial pressure and heart rate, and these effects were blocked by the GABA(A) receptor antagonist, bicuculline. Preadministration of diazepam into the NTS potentiated the pressor actions of isoguvacine and had variable effects on heart rate changes. Flumazenil, a benzodiazepine antagonist, blocked the diazepam-induced potentiation of the pressor response to isoguvacine. The second protocol employed receptor autoradiography to examine the presence of DS and diazepam-insensitive (DI) GABA(A) receptors in the NTS. Autoradiography confirmed that DS GABA(A) receptors were present in the NTS; however, no measurable levels of DI GABA(A) receptors were detected. We conclude that GABA(A)-mediated integration of central autonomic control in the NTS is mediated solely by DS GABA(A) receptors.
Sujet(s)
Pression sanguine/effets des médicaments et des substances chimiques , Encéphale/physiologie , Diazépam/pharmacologie , Rythme cardiaque/effets des médicaments et des substances chimiques , Récepteurs GABA-A/physiologie , Noyau du tractus solitaire/physiologie , Marqueurs d'affinité , Animaux , Anxiolytiques/administration et posologie , Anxiolytiques/pharmacologie , Système nerveux autonome/effets des médicaments et des substances chimiques , Système nerveux autonome/physiologie , Autoradiographie , Azotures/métabolisme , Benzodiazépines/métabolisme , Diazépam/administration et posologie , Synergie des médicaments , Agonistes GABA/pharmacologie , Acides isonicotiniques/pharmacologie , Mâle , Microinjections , Rats , Rat Sprague-Dawley , Récepteurs GABA-A/effets des médicaments et des substances chimiques , Noyau du tractus solitaire/effets des médicaments et des substances chimiques , TritiumRÉSUMÉ
Neurosteroids bind to unique sites on the GABA(A) receptor complex and modulate receptor function. The effects of neurosteroids on GABA(A) receptors have been well characterized in forebrain regions. However, little is known about their effects on GABA(A) receptors in the medulla, especially those areas involved in autonomic reflex pathways. Stimulation of [3H]flunitrazepam binding to the GABA(A) receptor by two progesterone metabolites, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-OH-DHP) and 3beta-hydroxy-5alpha-pregnan-20-one (3beta-OH-DHP), was studied using autoradiographic methods in the medulla and cerebellum of female rats at estrus. [3H]Flunitrazepam binding was enhanced by 3alpha-OH-DHP in every nucleus examined in the medulla and cerebellum. This effect was stereoselective since 3beta-OH-DHP had no effect on binding in any region. No differences were observed in the degree of stimulation of [3H]flunitrazepam binding by 3alpha-OH-DHP among medullary brain regions. However, in the cerebellum, the stimulation of binding was significantly greater in the granular layer than in the molecular layer. Stimulation of [3H]flunitrazepam binding by 3alpha-OH-DHP in nuclei involved in the baroreflex pathways supports previous studies which report that neurosteroids modulate autonomic regulation of blood pressure. These actions may also underlie alterations in autonomic function during pregnancy.
Sujet(s)
Flunitrazépam/métabolisme , Modulateurs GABA/pharmacologie , Moelle allongée/effets des médicaments et des substances chimiques , Prégnanolone/pharmacologie , Récepteurs GABA-A/physiologie , Animaux , Autoradiographie , Femelle , Moelle allongée/métabolisme , Dosage par compétition , Rats , Rat Sprague-Dawley , Récepteurs GABA-A/effets des médicaments et des substances chimiques , TritiumRÉSUMÉ
We present the case of a 51-year-old patient with a 31-year history of psychiatric symptoms, craniocervical dystonia, bulbar dysfunction, and parkinsonism. His dystonic movements included blepharospasm, jaw opening and lingual dystonia, and spasmodic retrocollis. Psychiatric symptoms included psychosis and depression, with onset years before the movement disorder. After his death by aspiration, examination of his brain revealed abnormalities limited to the neostriatum. Staining of brain sections, including Holzer, glial fibrillary acidic protein, and immunohistochemical stain for calbindin D28k, revealed the presence of a mosaic pattern of gliosis with neuronal loss (sparing large neurons) within this region. The islands of tissue between stands of gliosis had a normal appearance. This patient represents only the fourth case (and first North American born) with a mosaic pattern of gliosis in the neostriatum. The clinical and pathologic features were similar in all four cases except that our patient was the first with prominent psychiatric symptoms and a more stable, less progressive course. Mosaicism has been described in the X-linked Filipino disorder Lubag. Occurrence in non-Filipino patients, such as ours, suggest that either Lubag can develop in non-Filipino families or that mosaicism is a nonspecific pathologic finding in some patients with idiopathic dystonia. Finally, our case reports the notion that craniocervical dystonia may result from neostriatal dysfunction.