Transient electromechanical dissociation in hypertrophic cardiomyopathy

We describe a patient with hypertrophic cardiomyopathy who experienced several episodes of syncopal attacks, in whom the mechanism was transient electromechanical dissociation.     

Dissociation as a Mediator of the Relationship Between Childhood Trauma and Nonsuicidal Self-Injury in Females: A Path Analytic Approach

New theoretical models of nonsuicidal self-injury (NSSI) postulate that symptoms subsequent to childhood maltreatment rather than childhood maltreatment itself may lead to engagement in NSSI. However, little is known concerning which specific syndromes serve as underlying mechanisms. In this study we sought to examine the mediating effects of dissociative, posttraumatic, and depressive symptoms, 3 often comorbid syndromes following childhood trauma. In addition, we aimed to assess differences between women with and without NSSI. A sample of 87 female inpatients with a history of childhood abuse and neglect was divided into 2 subgroups (NSSI: n = 42, no NSSI: n = 45). The assessment included measures of NSSI characteristics; adverse childhood experiences; and posttraumatic, dissociative, and depressive symptoms. The NSSI group reported significantly more cases of childhood maltreatment and higher levels of current dissociative, posttraumatic, and depressive symptoms than patients without NSSI. The results of a path analysis showed that only dissociation mediated the relationship between a history of child maltreatment and NSSI when all 3 psychopathological variables were included in the model. The findings point toward a strong and rather specific association between dissociative experiences and NSSI and therefore have important implications for clinical practice.     

The Roles of Emotion Dysregulation and Dissociation in the Association Between Sexual Abuse and Self-Injury Among Juvenile Justice–Involved Youth

To date, scholars have established associations among nonsuicidal self-injury and sexual abuse, posttraumatic stress symptoms, and dissociation. However, leading theoretical models of the mechanisms underlying the association between trauma and negative outcomes suggest a more parsimonious explanation in that deficits in emotion regulation may underlie these various risk factors for self-injury. This study examined whether sexual abuse was differentially associated with nonsuicidal self-injury over and above other forms of traumatic experiences and whether the association between sexual abuse and self-injury was statistically mediated by emotion dysregulation and dissociation. Participants included 525 youth (392 boys, 133 girls) recruited from the U.S. juvenile justice system who completed measures of self-reported trauma exposure, posttraumatic stress symptoms, dissociation, and emotion dysregulation. Results of a hierarchical regression demonstrated that sexual abuse predicted posttraumatic stress symptoms and self-injury over and above other forms of traumatic experiences. Results of bootstrapped mediation analyses indicated that emotion dysregulation and dissociation in combination were implicated in self-injury among youth. The results suggest that youth in the juvenile justice system who experience sexual abuse may be at risk for higher rates of posttraumatic stress symptoms and that self-injury may be particularly salient for youth who experience sexual abuse. Furthermore, the results shed light on the role that dissociation and emotion dysregulation play in the relation between sexual abuse and self-injury, suggesting that a larger framework of self-regulation may have both empirical and clinical utility in helping to understand the underlying processes at play in these associations.     

Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain,a novel recombinant single-chain factor VIII

Introduction

rVIII-SingleChain (CSL627), a novel recombinant coagulation factor VIII (FVIII), is under investigation in a phase I/III clinical programme (AFFINITY) for the treatment of haemophilia A. Non-clinical studies were conducted to investigate the pharmacokinetic/pharmacodynamic profile of rVIII-SingleChain in comparison with full-length recombinant FVIII.

Materials and Methods

Binding affinity of rVIII-SingleChain for von Willebrand factor was investigated by surface plasmon resonance analysis. The pharmacokinetic profile of rVIII-SingleChain was compared with a marketed full-length recombinant FVIII concentrate (Advate^®) in haemophilia A mice, von Willebrand factor knock-out mice, Crl:CD (SD) rats, rabbits and cynomolgus monkeys. Systemic FVIII activity or antigen levels were recorded. Procoagulant activity was measured in an FeCl₃-induced arterial occlusion model and by recording thrombin generation activity (ex vivo) after administration of 200–250 IU/kg rVIII-SingleChain or full-length FVIII to haemophilia A mice.

Results

rVIII-SingleChain displayed a high affinity for von Willebrand factor (K_D = 44 pM vs. 139 pM for full-length recombinant FVIII). In all animal species tested, rVIII-SingleChain had more favourable pharmacokinetic properties than full-length recombinant FVIII: clearance was decreased and area under the curve and terminal half-life were enhanced vs. full-length recombinant FVIII, while in vivo recovery and volume of distribution were equivalent. rVIII-SingleChain showed a prolonged thrombin generation potential and prolonged procoagulant activity vs. full-length recombinant FVIII in an FeCl₃-induced arterial occlusion model.

Conclusions

rVIII-SingleChain had a higher affinity for von Willebrand factor than full-length recombinant FVIII and displayed favourable pharmacokinetic/pharmacodynamic properties in non-clinical models.     

Fast rebinding increases dwell time of Src homology 2 (SH2)-containing proteins near the plasma membrane

Receptor tyrosine kinases (RTKs) control a host of biological functions by phosphorylating tyrosine residues of intracellular proteins upon extracellular ligand binding. The phosphotyrosines (p-Tyr) then recruit a subset of ～100 Src homology 2 (SH2) domain-containing proteins to the cell membrane. The in vivo kinetics of this process are not well understood. Here we use total internal reflection (TIR) microscopy and single-molecule imaging to monitor interactions between SH2 modules and p-Tyr sites near the cell membrane. We found that the dwell time of SH2 modules within the TIR illumination field is significantly longer than predictions based on chemical dissociation rate constants, suggesting that SH2 modules quickly rebind to nearby p-Tyr sites after dissociation. We also found that, consistent with the rebinding model, the effective diffusion constant is negatively correlated with the respective dwell time for different SH2 domains and the dwell time is positively correlated with the local density of RTK phosphorylation. These results suggest a mechanism whereby signal output can be regulated through the spatial organization of multiple binding sites, which will prompt reevaluation of many aspects of RTK signaling, such as signaling specificity, mechanisms of spatial control, and noise suppression.     

TRANCEFORMATIONS: HYPNOSIS IN BRAIN AND BODY

In this review, the role of hypnosis and related psychotherapeutic techniques are discussed in relation to the anxiety disorders. In particular, anxiety is addressed as a special form of mind/body problem involving reverberating interaction between mental and physical distress. The history of hypnosis as a therapeutic discipline is reviewed, after which neurobiological evidence of the effect of hypnosis on modulation of perception in the brain. Specific brain regions involved in hypnosis are reviewed, notably the dorsal anterior cingulate gyrus and the dorsolateral prefrontal cortex. The importance of hypnotizability as a trait, stable variability in hypnotic responsiveness, is discussed. Analogies between the hypnotic state and dissociative reactions to trauma are presented, and the uses of hypnosis in treating posttraumatic stress disorder, stressful situations, and phobias as well as outcome data are reviewed. Effects of hypnosis on control of somatic processes are discussed, and then effects of psychosocial support involving Supportive–Expressive Group Therapy and hypnosis on survival time for cancer patients are evaluated. The evidence indicates an important role for hypnosis in managing anxiety disorders and anxiety related to medical illness.     

Comparative effects of sevoflurane and propofol based general anaesthesia for elective surgery on memory

Introduction

Unconscious processing of words during general anaesthesia has been suggested. We used the process dissociation procedure (PDP) to test memory performance during sevoflurane and propofol anaesthesia in relation to hypnotic depth.

Material and methods

One hundred participants anaesthetised for elective surgery (50 with propofol and 50 with sevoflurane) and 50 non-anaesthetized listened to a list of words. The bispectral index (BIS) of the anaesthetised patients was recorded. Within 36 h after word presentation, memory was assessed using a word stem completion task, based on Buchner''s model applied on the PDP.

Results

There was evidence of memory for words presented during light (BIS 61-80) (p = 0.001) and adequate (BIS 41-60) (p = 0.008) but not deep anaesthesia (BIS 21-40) (p = 0.09). The PDP showed a significant implicit but not explicit memory contribution (mean total explicit memory scores: 0.04 ±0.07 in all BIS categories; mean implicit memory scores: 0.01 ±0.04, 0.1 ±0.08, and 0.05 ±0.09 at BIS = 21-40, 41-60, and 61-80, respectively). There was a statistically significant difference between the mean implicit memory score (I) of the propofol and sevoflurane group in the BIS category 41-60 in general (p = 0.016), and after incision (I_A.I.) (p = 0.005) in particular, with propofol depressing I more than sevoflurane in both cases. Memory performance of nonanaesthetized participants was better, with a higher contribution of explicit and a comparable contribution of implicit memory.

Conclusions

During general anaesthesia, implicit memory persists even in adequate hypnotic states. Sevoflurane affects the implicit memory of adequately anaesthetised subjects less than propofol.     

The Concept of Dissociation in Early Psychoanalytic Writers

ABSTRACT

The concept of dissociation in early psychoanalytic writing is examined in order to show the intimate connection between old and new theories and how they have been transformed through time and different models. Contemporary work on trauma and dissociation may be seen as an illustration of, and developing from, early psychoanalytic formulations on the organization of the personality. These pioneering ideas constitute an encompassing theory of the personality from which treatment of trauma is easily deduced. Psychoanalysis in the United States, which remained loyal to Freudian models, is contrasted with the British Object Relations School. The term, “dissociation,” has a variety of connotations: (1) observable clinical phenomena, i.e., symptoms; (2) a general principle of psychic organization; (3) loosely, several defense mechanisms; (4) a synonym for splitting, mainly within British Object Relations; and (5) the clinical presentation and psychodynamic understanding of multiple personality or dissociative identity disorder. This plurality of concepts may conspire against scientific integration, perpetuating a confusion between the differing uses. Alternatively, it can enrich our theories, provided we do not loose sight of the models that make terms meaningful. The various senses of the word, and the relevant theoretical frameworks, are illustrated with a case example.