Статті в журналах з теми "Dissociation de liaison"

RésuméLe transporteur de la sérotonine sodium-dépendant est associé à la membrane plasmatique des plaquettes et des terminaisons nerveuses sérotoninergiques et constitue le mécanisme physiologique d’inactivation de la sérotonine. Un déficit en sérotonine est associé à la pathophysiologie de la dépression, et il a été suggéré que des modifications du transporteur de la sérotonine pouvaient exister au moment des épisodes dépressifs. En particulier, le nombre de sites transporteurs pourrait être diminué sur les plaquettes sanguines de patients déprimés, et des résultats comparables ont été obtenus dans certaines régions du cerveau humain post-mortem. Les inhibiteurs tricycliques et nontricycliques de la capture de sérotonine sont des antidépresseurs efficaces. Cependant, il existe une période de latence de 2 à 3 semaines entre le début du traitement et l’effet thérapeutique maximal. C’est pourquoi les études consacrées aux propriétés biochimiques et à la caractérisation moléculaire du transporteur de la sérotonine sont d’un intérêt particulier. La capture de la sérotonine par le transporteur êeut être inhibée sélectivement par le citalopram, la paroxétine, l’indalpine, la fluoxétine et le SL 81 0385. Cet effet se traduit in vitro par une augmentation de la neurotransmission sérotoninergique comme on a pu le montrer pour la paroxétine et le SL 81 0385 sur la libération de sérotonine induite par stimulation électrique dans des coupes de cortex frontal humain. Les dérivés marqués inhibiteurs de la capture tels que l’imipramine-[3H], la paroxétine-[3H] et le citalopram-[3H] ont été utilisés comme ligands spécifiques pour caractériser le transporteur. Dans les expériences de dissociation de la liaison de la paroxétine-[3H] aux membranes de cortex cérébral de rat, le citalopram, l’indalpine, la fluoxétine, le SL 81 0385, l’imipramine et la sérotonine ont des valeurs de 1½ de dissociation similaires à celle obtenue pour la paroxétine. De plus, le SL 81 0385, la fluoxétine, l’imipramine et la sérotonine induisent une protection contre l’inactivation de la liaison de la paroxétine-[3H] par le N-éthylmaléimide aux membranes de cortex cérébral de rat. Ces résultats suggèrent que le domaine de liaison des inhibiteurs tricyliques et non-tricycliques de la capture de sérotonine correspond à un site d’exclusion mutuelle par rapport au site de reconnaissance du substrat. Le transporteur neuronal de la sérotonine des membranes de cortex cérébral de rat a été solubilisé et purifié par chromatographie d’affinité sur une résine agarose à laquelle un dérivé du citalopram a été fixé par liaison covalente. La liaison de la paroxétine-[3H] à la préparation purifiée est caractérisée par un Kd de 0.71 nM et un Bmax supérieur à 1 962 pmol/mg de protéines. La purification du transporteur se traduit par un accroissement de plus de 3 000 fois de l’activité de la liaison de la paroxétine-[3H] par rapport à celle de la préparation membranaire initiale. Le profil pharmacologique de la liaison de la paroxétine-[3H] à cette préparation purifiée est préservé puisque les valeurs de Ki pour le citalopram, l’imipramine et la sérotonine sont respectivement de 19 nM, 80 nM et 3,5 μM, comparables aux Ki de ces composés sur la liaison de la paroxétine-[3H] aux membranes de cortex cérébral de rat. La purification du transporteur ainsi obtenue est la première étape qui doit permettre d’analyser les propriétés fonctionnelles du transporteur au niveau moléculaire.

Partant de la thèse selon laquelle le modèle social-démocrate, consistant en une liaison organique d’un parti politique et d’une confédération syndicale, représente à la fois le modèle le plus puissant en son effet – par le nombre de ses membres et sa structuration – et le plus socialiste en son principe organisationnel – puisqu’il consacre l’union du travailleur et du citoyen, plutôt que sa dissociation –, nous plaidons ici pour la fondation d’une « social-démocratie » française, à partir de la reconfiguration sociale et politique actuelle.

La pharmacocinétique de la sulfaméthoxypyridazine (SMPD) a été étudiée chez le dromadaire après administrations intraveineuse et orale. Les résultats obtenus, après injection intraveineuse, indiquent que la cinétique de cet antibactérien suit un modèle à deux compartiments. Le volume de distribution (Vss) de 0,47 l/kg suggère que la SMPD est essentiellement diffusée dans le compartiment vasculaire et les tissus hautement vascularisés. La demi-vie d'élimination [t1/2(ß)] et la clearance plasmatique (CL) ont des valeurs moyennes respectives de 9,5 h et 0,037 l/kg.h. Quant à l'administration orale, la concentration maximale du produit n'a été atteinte qu'après un délai de 17 h et la biodisponibilité absolue a été de l'ordre de 57 % Enfin, l'étude de la liaison de la SMPD aux protéines plasmatiques du dromadaire a montré que la fixation variait de 47 à 72 % et qu'elle dépendait de la concentration du médicament. La constante de dissociation à l'équilibre (Kd) a été de 196 µg/ml et la capacité maximale de fixation a été de l'ordre de 335 µg/ml.

Abstract Recent studies have shown a suboptimal humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients diagnosed with hematologic malignancies; however, data about cellular immunogenicity are scarce. The aim of this study was to evaluate both the humoral and cellular immunogenicity 1 month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by using the Elecsys and LIAISON anti–SARS-CoV-2 S assays, and T-cell response was assessed by using interferon-γ release immunoassay technology. Overall, 76.3% (184 of 241) of patients developed humoral immunity, and the cellular response rate was 79% (184 of 233). Hypogammaglobulinemia, lymphopenia, active hematologic treatment, and anti-CD20 therapy during the previous 6 months were associated with an inferior humoral response. Conversely, age >65 years, active disease, lymphopenia, and immunosuppressive treatment of graft-versus-host disease (GVHD) were associated with an impaired cellular response. A significant dissociation between the humoral and cellular responses was observed in patients treated with anti-CD20 therapy (the humoral response was 17.5%, whereas the cellular response was 71.1%). In these patients, B-cell aplasia was confirmed while T-cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients undergoing immunosuppressive treatment of GVHD, whereas only 52.4% had a cellular response. The cellular and humoral responses to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematologic malignancies are highly influenced by the presence of treatments such as anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

Les AVP sont le principal pourvoyeur d’ESPT (Kupchik et al., 2007), dont la prévalence fluctue de 6 à 45 % entre les études (Heron-Delaney et al., 2013). En l’absence de repérage clinique, l’ESPT peut se chroniciser (Kessler et al., 1995). Les outils actuels permettent son diagnostic (Jackson et al., 2011), mais pas de dépister précocement les sujets à risque de développer un ESPT post-AVP en aigu (8 semaines) comme en chronique (6 mois) ou en tardif (1 an). Nous présentons une étude longitudinale réalisée sur 274 patients répartis sur 6 centres de traumatologie ayant pour objectif principal de valider un outil infirmier de dépistage précoce d’ESPT après un AVP (DEPITAC). Dix questions ont été soumises à tout patient hospitalisé dans les 15 jours après un AVP, ainsi qu’une PDI et un MINI DSM-IV. La PCL-S (cut-off à 44) a permis le diagnostic à 8 semaines, 6 mois et 1 an. L’analyse statistique a été réalisée avec le logiciel SAS Institute 9.4. Le score total DEPITAC était significativement associé au diagnostic d’ESPT à 1 an (OR : 1,43 ; IC95 % : 1,14–1,79) avec un pouvoir discriminant de 0,64 (IC95 % : 0,56–0,72). DEPITAC était corrélé à l’échelle PDI (p < 0,0001) avec un faible coefficient de corrélation (r = 0,32) montrant une faible redondance. Seules 3 questions après analyses bivariées s’avèrent significatives : « présence d’autres blessés ou décédés lors de l’AVP », « présence d’une dissociation post-AVP » et « s’être vu mourir lors de l’AVP » avec un pouvoir discriminant de 0,65 (IC95 % : 0,57–0,73). Aucun effet centre n’a été mis en évidence (p = 0,90). Nos résultats semblent montrer qu’à l’aide de seulement 3 questions de dépistage, les équipes infirmières pourraient repérer les patients à risque de développer un ESPT aigu ou tardif, leur permettant ainsi d’alerter précocement les équipes psychiatriques de liaison ou de pschotraumatologie.

The paper reports a descriptive survey of the referrals received by a new psychiatric liaison service in Rawalpindi in the first 2 years. The survey showed a rapid increase in use of the service, particularly by the emergency department. There was a lower proportion of referrals for self-harm and substance misuse than occurs in similar services in high-income countries but a higher proportion of patients presenting with dissociative (conversion) disorders. The large proportion of patients who had abnormal findings on physical examination remains unexplained and warrants further investigation.

Psychiatric co-morbidity in patients with physical illness is known to influence the course and outcome of both conditions. Consultation liaison psychiatry [CLP] can be regarded as an essential service between psychiatry and other medical specialties. Efficient communication between different levels of care is known to have an impact on the quality of health care. To study the patterns of referrals to the department of psychiatry and diagnostic concordance between referring physicians to CL-Psychiatrist.The present study was a cross-sectional study conducted in the Department of Psychiatry of a tertiary care hospital. All the patients referred to the Psychiatry department for 4 months were taken after excluding referrals sent for disability assessment. Socio-demographic details, source of referral, reason for referral, and the psychiatric diagnosis by both the referring doctor and CL-psychiatrist were recorded. Statistical analysis was done using SPSS 25.0 software and kappa value was used to estimate the diagnostic concordance.In the sample of 100 referrals studied, the mean age of the sample was 40.96±13.42 years. The majority of the cases referred were inpatients (61%), from the department of general medicine and allied branches (85%), (General medicine -55, Neurology- 21). The most common diagnosis was alcohol dependence syndrome 24 (24%), followed by depression (18%) and phobic anxiety (18%).The concordance of the diagnosis between the referral and the psychiatry team was in perfect agreement (κ=0.81- 1.00) for paranoid schizophrenia, bipolar affective disorder, delirium, dissociative disorder, delusional disorder, and alcohol dependence syndrome. Very low concordance was observed in diagnosing obsessive-compulsive disorder (k=0) and adjustment disorder (k=0).The overall diagnostic concordance was poor for adjustment disorder, OCD, and vascular dementia, and good for paranoid schizophrenia, delirium, dissociative disorder, delusional disorder, and BPAD.

RésuméOn se propose de montrer comment l’émergence d’un nouveau paradigme en psychologie – la psychologie cognitive, son extension à l’étude de l’anxiété – offre par rapport à deux modéles dominants – la théorie de l’apprentissage et la psychanalyse – une troisième voie de recherche. Parmi les acceptions du terme «cognitif», c’est l’idée d’une organisation des niveaux expressifs qui est retenue. Partant d’une définition de l’anxiété en termes de conséquence comportementale d’un faisceau d’interactions, on montre à l’appui de méthodes neuropsychologiques élargies: – l’existence de dissociations entre niveaux expressifs en insistant sur le degré de liberté et l’hétérogénéité de fonctionnement qui en découlent; – l’existence de formes d’indépendance ou d’interdépendance entre niveaux expressifs, en évoquant les controverses sur le caractére automatique ou volontaire des liaisons entre expressions faciales et les autres niveaux expressifs, verbaux et psychophysiologiques; – le rôle privilégié du langage en tant que fonction intégratrice des autres niveaux expressifs. En conclusion, on souligne que la spécificité de l’anxiété au sein du systèmé général des émotions consiste essentiellement dans son caractère non modulaire.

Background Dissociative (non-epileptic) seizures are potentially treatable by psychotherapeutic interventions; however, the evidence for this is limited. Objectives To evaluate the clinical effectiveness and cost-effectiveness of dissociative seizure-specific cognitive–behavioural therapy for adults with dissociative seizures. Design This was a pragmatic, multicentre, parallel-arm, mixed-methods randomised controlled trial. Setting This took place in 27 UK-based neurology/epilepsy services, 17 liaison psychiatry/neuropsychiatry services and 18 cognitive–behavioural therapy services. Participants Adults with dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous year and meeting other eligibility criteria were recruited to a screening phase from neurology/epilepsy services between October 2014 and February 2017. After psychiatric assessment around 3 months later, eligible and interested participants were randomised between January 2015 and May 2017. Interventions Standardised medical care consisted of input from neurologists and psychiatrists who were given guidance regarding diagnosis delivery and management; they provided patients with information booklets. The intervention consisted of 12 dissociative seizure-specific cognitive–behavioural therapy 1-hour sessions (plus one booster session) that were delivered by trained therapists, in addition to standardised medical care. Main outcome measures The primary outcome was monthly seizure frequency at 12 months post randomisation. The secondary outcomes were aspects of seizure occurrence, quality of life, mood, anxiety, distress, symptoms, psychosocial functioning, clinical global change, satisfaction with treatment, quality-adjusted life-years, costs and cost-effectiveness. Results In total, 698 patients were screened and 368 were randomised (standardised medical care alone, n = 182; and cognitive–behavioural therapy plus standardised medical care, n = 186). Primary outcome data were obtained for 85% of participants. An intention-to-treat analysis with multivariate imputation by chained equations revealed no significant between-group difference in dissociative seizure frequency at 12 months [standardised medical care: median of seven dissociative seizures (interquartile range 1–35 dissociative seizures); cognitive–behavioural therapy and standardised medical care: median of four dissociative seizures (interquartile range 0–20 dissociative seizures); incidence rate ratio 0.78, 95% confidence interval 0.56 to 1.09; p = 0.144]. Of the 16 secondary outcomes analysed, nine were significantly better in the arm receiving cognitive–behavioural therapy at a p-value < 0.05, including the following at a p-value ≤ 0.001: the longest dissociative seizure-free period in months 7–12 inclusive post randomisation (incidence rate ratio 1.64, 95% confidence interval 1.22 to 2.20; p = 0.001); better psychosocial functioning (Work and Social Adjustment Scale, standardised treatment effect –0.39, 95% confidence interval –0.61 to –0.18; p < 0.001); greater self-rated and clinician-rated clinical improvement (self-rated: standardised treatment effect 0.39, 95% confidence interval 0.16 to 0.62; p = 0.001; clinician rated: standardised treatment effect 0.37, 95% confidence interval 0.17 to 0.57; p < 0.001); and satisfaction with treatment (standardised treatment effect 0.50, 95% confidence interval 0.27 to 0.73; p < 0.001). Rates of adverse events were similar across arms. Cognitive–behavioural therapy plus standardised medical care produced 0.0152 more quality-adjusted life-years (95% confidence interval –0.0106 to 0.0392 quality-adjusted life-years) than standardised medical care alone. The incremental cost-effectiveness ratio (cost per quality-adjusted life-year) for cognitive–behavioural therapy plus standardised medical care versus standardised medical care alone based on the EuroQol-5 Dimensions, five-level version, and imputed data was £120,658. In sensitivity analyses, incremental cost-effectiveness ratios ranged between £85,724 and £206,067. Qualitative and quantitative process evaluations highlighted useful study components, the importance of clinical experience in treating patients with dissociative seizures and potential benefits of our multidisciplinary care pathway. Limitations Unlike outcome assessors, participants and clinicians were not blinded to the interventions. Conclusions There was no significant additional benefit of dissociative seizure-specific cognitive–behavioural therapy in reducing dissociative seizure frequency, and cost-effectiveness over standardised medical care was low. However, this large, adequately powered, multicentre randomised controlled trial highlights benefits of adjunctive dissociative seizure-specific cognitive–behavioural therapy for several clinical outcomes, with no evidence of greater harm from dissociative seizure-specific cognitive–behavioural therapy. Future work Examination of moderators and mediators of outcome. Trial registration Current Controlled Trials ISRCTN05681227 and ClinicalTrials.gov NCT02325544. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 43. See the NIHR Journals Library website for further project information.

AbstractObjective: The aim of this study was to investigate the characteristics of patients whose identities are unknown at presentation to psychiatric services.Method: We retrospectively reviewed 12 years of presentations to an emergency psychiatric unit and identified 37 anonymous presentations in that period. Cases were assessed with regard to demographic data, legal status, reasons for presentation, putative diagnosis at presentation, eventual documented (ICD-9) diagnosis, previous history, duration of anonymity, method of identification and re-occurrence.Results: 0.6% of all patients who presented during the study period were unidentified for at least 24 hours. Patients were young (mean age 33.6 years). Over half were of foreign nationality (53%). The majority were suffering from major psychotic illnesses (86%). When compared with all admissions during the study period, schizophrenia and drug-induced psychoses were significantly more common in the group unidentified at presentation. Malingering, organic psychiatric disorders and dissociative states were not commonly encountered underlying diagnoses. All of our patients were subsequently identified. Successful identification methods included self admission, careful examination of personal belongings, careful history taking, liaison with police and recognition by staff. Patients frequently had a previous psychiatric history (91%). Recurrence was uncommon.Conclusion: The anonymous presentation represents a unique challenge to the investigative skills of the psychiatrist. The application of basic strategies enables the successful identification of the majority of cases.

Background: Mental health and its related problems are growing concerns over the world. The early onset of emotional and behavioral problem in the young children is related to a variety of health and behavior problems in adolescence and later life as well. Most of these children present to Pediatric outpatient clinics owing to the Stigma and lack of awareness. The aim of the study is to find out the pattern and prevalence of psychiatric morbidity in children presenting to pediatric outpatient clinics.Methods: It is a cross sectional, point prevalence study of children who have attended Child Guidance Clinic of Pediatric Department in a tertiary care teaching hospital October 2019 to January 2020. Clinical and demographic details was collected in a semi-structured proforma and the details were analyzed.Results: A total of 114 children were analyzed during the study period and this study comprised of 62 boys and 52 girls. Most of the children belonged to the age group of 11-15 years (51%) followed by the ages of 6-10(29.8%). Most common reason for consultation was change in behavior, school refusal and poor academic performance. The most common diagnosis made was Dissociative Conversion Disorder (17.6%), Nocturnal enuresis (15.7%), Mild Mental Retardation (10.5%) and Seizure Disorder with Behavioral Problems (10.5%).Conclusions: A significant number of children attending the Paediatric OPD of general hospitals have psychiatric disorders. The emotional and behavioral problems in children often present with physical symptoms. An effective liaison of services will help to identify and treat children with psychiatric morbidity.

ObjectiveThere is currently limited research exploring healthcare professionals’ (HCPs) experiences of working with patients with dissociative seizures (DS). Existing studies do not focus on the role of psychiatrists in treating this complex condition. The objective of this study was to gain an understanding of UK-based psychiatrists’ experiences of the DS patient group. Against the backdrop of a UK-wide randomised controlled trial (RCT), the focus was broadened to encompass issues arising in everyday practice with the DS patient group.Design, participants and methodsA qualitative study using semistructured interviews was undertaken with 10 psychiatrists currently working with DS patients within the context of a large RCT investigating treatments for DS. Thematic analysis was used to identify key themes and subthemes.SettingThe psychiatrists were working in Liaison or Neuropsychiatry services in England.ResultsThe key themes identified were other HCPs’ attitudes to DS and the challenges of the DS patient group. There is a clear knowledge gap regarding DS for many HCPs and other clinical services can be reluctant to take referrals for this patient group. Important challenges posed by this patient group included avoidance (of difficult emotions and help), alexithymia and interpersonal difficulties. Difficulties with alexithymia meant DS patients could struggle to identify triggers for their seizures and to express their emotions. Interpersonal difficulties raised included difficulties in attachment with both HCPs and family members.ConclusionsA knowledge gap for HCPs regarding DS has been identified and needs to be addressed to improve patient care. Given the complexity of the patient group and that clinicians from multiple disciplines will come into contact with DS patients, it is essential for any educational strategy to be implemented across the whole range of specialties, and to account for those already in practice as well as future trainees.Trial registration numberISRCTN05681227;NCT02325544; Pre-results.

Background: More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited. Objectives: The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts. Design: Systematic review. Data Sources and methods: PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed. Results: We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments. Conclusion: Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.

AbstractConsultation liaison psychiatrists are frequently asked to evaluate patients with altered mental status (AMS). Psychiatrists have unique perspectives and approaches to care for confused patients, particularly optimizing facilitation of care and maintaining vigilance for diagnostic overshadowing. Psychiatrists also offer expertise in primary psychiatric illnesses that can overlap with AMS, and the most common etiology of AMS is delirium. In this article, we provide a consultation liaison psychiatrist perspective on AMS and related psychiatric conditions in addition to delirium. Manic and psychotic episodes have primary and secondary etiologies, with some symptoms that can overlap with delirium. Catatonia, neuroleptic malignant syndrome, and serotonin syndrome are potentially fatal emergencies, and require prompt index of suspicion to optimize clinical outcomes. Trauma sequelae, functional neurologic disorders, and dissociative disorders can present as puzzling cases that require psychiatric facilitation of care. Additionally, AMS is sometimes due to substance intoxication and withdrawal in the hospital. A nonstigmatizing approach to evaluation and management of delirium and AMS can ensure optimal patient care experiences and outcomes.