Les structures cliniques et la sublimation

According to the teachings of Jacques Lacan, we are able to join three clinical structures – hysteria, obsessional neurosis and paranoia – with three terms of sublimation – art, religion and science. Similarly, we are able to unite them with three psychical operations – repression, displacement and foreclosure – and with three states of the void – organisation, shunning and unbelief. As a result, we study why and how art, which is similar to hysteria, can organize the void which has previously been repressed; why and how religion, which is similar to obsessional neurosis, avoids it and displaces it; and finally why and how science, which is similar to paranoia, disbelieves in the void that has been previously barred. While studying the definitions of Freudian sublimation, we try to clarify the relationship between these three clinical structures and the Lacanian formula of sublimation: the elevation of an object to the dignity of the Thing. Our interest is to demonstrate that the Lacanian perspective assigns a clinic of sublimation whose interest lies in a treatment of the void of the Thing.     

Mélancolie délirante et paranoïa : diagnostic différentiel

Objectives

In this paper, the author proposes to separate delirious melancholy and paranoia, locating in these two psychoses the common points and points which are able to distinguish them clearly.

Methodology

We present the delirious melancholy according to the psychiatrist H. Ey's theory, then – with psychoanalytical approach, according notably to Lacan – we will underline three important points of reference: relationships with “fault”, with the “object”, and finally with the “Other” (Lacan).

Results

These three points will lead us to the melancholic self-accusation and to the paranoiac accusation, to the position of “exception”, and to delirious common themes.

Discussion and conclusion

Finally, we attempt to ascertain – as Freud formulated about paranoiac delirium – whether melancholic delirium could also be a “tentative of (self) cure”.     

Intention and planning predicting medication adherence following coronary artery bypass graft surgery

Objective

Medication adherence rates after coronary artery bypass graft (CABG) surgery are low due to intentional (e.g., deliberately choosing not to take medication) and unintentional (e.g., forgetting to take the medication) person-related factors. There is a lack of studies examining the psychological factors related to non-adherence in CABG patients. Intentions to take medication and planning when, where, and how to take medication and to overcome unintentional forgetting to take medication were hypothesized to be independently related to medication adherence. Furthermore, planning to overcome forgetting was hypothesized to be more strongly associated with medication adherence in patients who have stronger intentions to take medication, reflecting the idea that planning is a factor that specifically helps in patients who are willing to take medication, but fail to do so.

Methods

Measures of medication adherence, intention and planning were collected in a sample of (N = 197) post-CABG surgery patients followed from discharge (baseline; Time 1) over a 12-month period (Time 2) in Boo-Ali Hospital in Qazvin, Iran. A series of hierarchical multiple regression analyses were performed in which medication adherence at Time 2 was regressed onto socio-demographic and clinical factors, the hypothesized psychological variables (adherence-related intention and planning), and interaction terms.

Results

Intentions to take medication (B = .30, P < .01), action planning when, where, and how to take the medication (B = .19, P < .01), and coping planning how to avoid forgetting to take the medication (B = .16, P < .01) were independently related to medication adherence. Beyond that, action planning × intention to take medication (B = .06, P < .05) and coping planning × intention (B = .07, P < .01) interaction also significantly predicted adherence.

Conclusion

Intention to take medication was associated with better medication adherence and action and coping planning strategies to avoid forgetting to take the medication added significantly to the prediction of adherence in the year following CABG discharge. This is in line with theory and evidence about the independent roles of intentional and unintentional predictors of non-adherence. As hypothesized, planning to overcome unintentional forgetting to take the medication was more predictive of medication adherence in those patients who reported higher intentions to take medication, reflecting the idea that planning helps patients overcome unintentional reasons of being non-adherent.     

Psychiatrie et ordre public,de l’Ancien Régime à la Restauration. L’exemple parisien

In the discussions relative to the vote of the 1838 law, the Minister of the Interior emphasized that “to dispose of furious and insane persons” and to make society “safe from the excesses of a delirious head” is more than a right for a government, “it is one of its most imperious duties” which has been conferred to it “from time immemorial”. As a matter of fact, for more than a hundred and fifty years, the public authority had had at its disposal the means to respond to emergency situations and to public disorders caused by insane persons. Under the Ancien Regime it was the Lieutenant General of Police, guarantor of order in all matters, who had the power of ordering their immediate legal admission in an institution, so as to be “taken care of and medicated until perfect recovery”. At the beginning of the Revolution, the abolition of sales of public offices, the suppression of the jurisdiction of the Châtelet, the abolition of “lettres de cachet” opened up a rather confused decade as witnessed by the archives of the General Police. However, the successive administrations will dispose of the police laws of 1790 and 1791 relative to the “insane and furious” and to the “regrettable events” they could cause. The Consulate marks a decisive step with the establishment of the prefectoral administration, the adoption of the Civil Code, the creation of the General Council of Hospices with its Central Bureau, and with the reform of the establishments: The closing of the Hôtel-Dieu rooms, the reform of the Charenton Institution and the installation of treatment services at La Salpêtrière then at Bicêtre. The Police Headquarters, a Parisian specificity, will thus dispose of the means to isolate the insane who cause public disorders or who threaten public safety and to impose their admission, upon medical advice, into “hospitals established for the treatment of madness”.     

Effect of antiepileptic drug polytherapy on urinary pH in children and young adults

Objects  The relationship between antiepileptic drugs (AEDs) polytherapy and urinary pH was studied to demonstrate the effect and difference of AED polytherapy compared to monotherapy. Materials and methods  A total of 271 urine samples from patients receiving AED polytherapy aged from 7 months to 35 years were enrolled. Two AEDs were co-administered to 215 patients, three AEDs to 45 patients, four AEDs to ten patients, and five AEDs to one patient. Results  The distribution of urinary pH shifted to the alkaline range with increasing numbers of co-administered AEDs (p < 0.0001). The distribution of urinary pH shifted to the alkaline side with AED polytherapy that included valproate (p < 0.05) or acetazolamide (p < 0.03). The distribution of urinary pH did not change with or without zonisamide, carbamazepine, phenobarbital, phenytoin, or clonazepam. Conclusions  Urinary pH should be monitored in patients receiving AED polytherapy, particularly those receiving valproate, acetazolamide, or various AEDs in combination.     

Reduced eye gaze explains "fear blindness" in childhood psychopathic traits

ObjectiveDamage to the amygdala produces deficits in the ability to recognize fear due to attentional neglect of other people's eyes. Interestingly, children with high psychopathic traits also show problems recognizing fear; however, the reasons for this are not known. This study tested whether psychopathic traits are associated with reduced attention to the eye region of other people's faces.MethodAdolescent males (N = 100; age mean 12.4 years, SD 2.2) were stratified by psychopathic traits and assessed using a Tobii eye tracker to measure primacy, number, and duration of fixations to the eye and mouth regions of emotional faces presented via the UNSW Facial Emotion Task.ResultsHigh psychopathic traits predicted poor fear recognition (1.21 versus 1.35; p < .05) and lower number (1.85 versus 2.51; p < .001) and duration (375 versus 620 ms; p < .001) of eye fixations, and fewer first foci to the eye region (1.01 versus 2.01; p < .001). There were no differences in gaze indices to the mouth region. All indices of gaze to the eye region correlated positively with accurate recognition of fear for the high psychopathy group, especially the number of times that subjects looked at the eyes first (r = .50; p < .01).ConclusionsAttention to other people's eyes is reduced in young people with high psychopathic traits, thus accounting for their problems with fear recognition, and is consistent with amygdala dysfunction failing to promote attention to emotional salience in the environment.     

Oligoclonal bands and MRI in clinically isolated syndromes: predicting conversion time to multiple sclerosis

The objective of the study was to evaluate whether the presence of oligoclonal bands (OB) adds information in predicting CIS conversion to clinical definite multiple sclerosis (CDMS) and conversion time to CDMS. From 1998 to 2006, CIS patients were included in a prospective study. Patients underwent brain MRI and OB determination within 2 months of the first demyelinating event. We analyzed conversion to CDMS and time to conversion to CDMS according to abnormal MRI and the presence of OB. Forty patients were included. Fifteen patients (37%) converted to CDMS; 14 of them (93.3%) had abnormal baseline MRI (P = 0.01, RR = 5.9; 95% CI 1.3–10.1) and 13 (86.7%) had positive OB in CSF (P = <0.01, RR = 5.3; 95% CI 1.6–9.5). The risk of conversion to CDMS in patients with positive OB and abnormal baseline MRI was significantly higher compared to patients negative for both tests or with only one positive (RR = 9.1; 95% CI 3.5–14.6). Time to conversion to CDMS was 6.8 ± 3.5 months for patients with OB and abnormal baseline MRI and 19 ± 14 months for patients with only one abnormal test. CIS patients with abnormal baseline OB in CSF have a higher risk for developing CDMS. Regarding conversion time to CDMS, when abnormal MRI was added to positive OB, patients converted faster (mean time, 6 vs. 19 months). This information may be useful when considering treatment in CIS patients.     

Big five-factor contributions to addiction to alcohol

Introduction

Personality in the field of addiction has been the subject of many studies. The purpose of this article is to synthesize the data obtained with the Neuroticism Extraversion Openness – Personality Inventory – Revised (NEO-PI-R) and the NEO – Five-Factor Inventory (NEO-FFI) among the persons who drink and suffer from addiction to alcohol.

Background

These tools, based on the theory of “The Big Five Factors”, assess the personality from a dimensional point of view. The five big dimensions addressed by these tools, are “Neuroticism” (general tendency to experience negative feelings), “Extraversion” (sociability, positive feelings, activity and self-confidence), “Openness” (imagination, intellectual curiosity, aesthetic sensitivity, attention paid to one's own feelings and no dogmatic behavior), “Agreeableness” (interpersonal tendencies) and “Conscientiousness” (forward planning, organization and task carrying out). According to Diagnostic and Statistical Manual of mental disorders (DSM-IV-TR), alcohol consumption is based on three dissimilar behaviors: utilization (alcohol consumption not leading to complications or damage), abuse (regular consumption likely to cause somatic, psycho-emotional or social damage for the individual or for his/her family circle) and dependency (excessive utilization leading to deterioration in functioning or clinically significant suffering).

Literature findings

Alcohol consumption among young adults can thus be predicted through a high level of “Neuroticism” associated with a low level of “Agreeableness”. Persons having been addicted to alcohol (present or past) have a high level of “Neuroticism”, a low “Agreeableness” and a low level of “Conscientiousness”, contrary to patients who have never been addicted to alcohol. The NEO-PI-R also enables a more accurate analysis of the personality, since each of these five big dimensions is divided into six facets. Among the patients with a past or present diagnosis of alcohol abuse, we found a low score on facets “trust”, “achievement striving”, “self-discipline” and “dutifulness” and a high score on “impulsiveness”, “vulnerability”, and “excitement-seeking”. Although dimension and facet results measured by this tool can differ according to craving level or according to gender, the studies agree in that there are common aspects among the patients.     

Prevent breaking bad: A proof of concept study of rebalancing the brain's rumination circuit with real‐time fMRI functional connectivity neurofeedback

Rumination, repetitively thinking about the causes, consequences, and one''s negative affect, has been considered as an important factor of depression. The intrusion of ruminative thoughts is not easily controlled, and it may be useful to visualize one''s neural activity related to rumination and to use that information to facilitate one''s self‐control. Real‐time fMRI neurofeedback (rtfMRI‐nf) enables one to see and regulate the fMRI signal from their own brain. This proof‐of concept study utilized connectivity‐based rtfMRI‐nf (cnf) to normalize brain functional connectivity (FC) associated with rumination. Healthy participants were instructed to brake or decrease FC between the precuneus and the right temporoparietal junction (rTPJ), associated with high levels of rumination, while engaging in a self‐referential task. The cnf group (n = 14) showed a linear decrease in the precuneus‐rTPJ FC across neurofeedback training (trend [112] = −0.180, 95% confidence interval [CI] −0.330 to −0.031, while the sham group (n = 14) showed a linear increase in the target FC (trend [112] = 0.151, 95% CI 0.017 to 0.299). Although the cnf group showed a greater reduction in state‐rumination compared to the sham group after neurofeedback training (p < .05), decoupled precuneus‐rTPJ FC did not predict attenuated state‐rumination. We did not find any significant aversive effects of rtfMRI‐nf in all study participants. These results suggest that cnf has the capacity to influence FC among precuneus and rTPJ of a ruminative brain circuit. This approach can be applied to mood and anxiety patients to determine the clinical benefits of reduction in maladaptive rumination.     

Relationship between clinical examination, Quality of Life, disability and depression in CMT patients: Italian Multicenter study

Objective  To assess which are the clinical examination tests that are more related to quality of life (QoL), depression, and disability in CMT patients. Design  Large prospective multicenter study through the use of validated clinical, disability, and QoL measurements. Correlations between clinical pattern and disability/QoL and depression were studied. Setting  Departments of Neurology. Patients and participants  211 CMT patients (60% females, mean age 42.5 years). Interventions  None. Measurements and results  Sensory function was related to both mental and physical aspects of patient’s QoL. Ability to walk on toes and heels was related to physical aspects of QoL/disability but also to bodily pain. Strength of forearm/hand intrinsic muscles was related to disability and physical aspects of QoL. Conclusions  Some clinical tests may be better outcome measures than others because they are related to aspects of life highly relevant to the patients. This information may be useful in clinical practice and in clinical trials to infer the patient’s QoL.     

Functional (neurologic) recovery following transient focal cerebral ischemia in the rat requires at least 80% of ipsilateral cortical and subcortical integrity

Though many drugs have been proven to reduce ischemia-induced brain damage in animal models, most of them have failed to reach clinical trials or, if not, have not been proven to be efficient in humans suffering stroke. Here, by performing a global analysis of recently published data in eighty nine rats subjected to middle cerebral artery occlusion (MCAO)-induced transient focal cerebral ischemia, we show that the ability of the animals to recover motor function is dependent on and highly correlated to their percentage of healthy cortex (r = 0.973; P < 0.001) and healthy subcortical brain structures (r = 0.916; P < 0.001). In addition, data analysis further reveals that neuroprotection requires preserving at least 80% and 90% of the integrity of the ipsilateral hemispheris subjected to MCAO to provide partial and full functional neurologic recovery, respectively. We suggest that this should be taken into account in preclinical pharmacological studies to estimate the actual potentially clinical interest of drugs developed for neuroprotection as well as to avoid developing further research on drugs that only provide mild to moderate histologic outcome.     

Élaboration méthodologique dans la conception d’un dispositif thérapeutique de groupe en institution

ObjectivesThis article highlights how the creation of a group psychotherapeutic setting in an institution constitutes a subject of elaboration before the clinical experience itself. Our hypothesis is that the psychotherapeutic dimension and the dynamic power of a group are determined by the conception that clinicians have of their setting.MethodUsing the examples of several clinical situations (in an institutional setting) that we either created or inherited, we have distinguished different fields or objects of analysis. These objects are in mutual interface and make the therapeutic project a creation of the clinician.ResultsDifferent relationships can thus constitute internal obstacles to the creation and implementation of different types of therapy. We will distinguish: – the relationship of clinicians to their team and to their institution; – the relationship of the therapeutic project to the institutional framework; – the relationship of the therapeutic project to the different groups to which clinicians belong; – that of clinicians to their customary field of practice.DiscussionThe examples proposed here show how, according to the conditions of specific arrangements between clinicians, their professional affiliations, their team and the institutional situation, different points may appear as elements of suffering, confusion, or conflicts to be elaborated, discriminated, or resolved.ConclusionThe elements that make up the clinician's conception of their therapeutic initiative do not necessarily need to be explored before the project's implementation but potentially constitute objects of elaboration that might appear before or in the early stages of the clinical experience.     

Étude de faisabilité d’une exposition thérapeutique en réalité virtuelle pour joueurs pathologiques

The experiment presented is the result of a partnership between the Paris-Nanterre University (CLIPSYD laboratory, EA 4430) and the CSAPA Imagine (Simone Veil Hospital, GH Eaubonne-Montmorency). Virtual reality immersion exposure for pathological gamblers is beneficial in the context of cognitive and behavioral interventions. It can be used to evoke the desire to play and to have access to automatic thoughts and mistaken beliefs of the players when they find themselves in a gambling context. Exposure is used until the urge to play diminishes and disappears which is the process of desensitization or extinction.ObjectiveThe objective of the study was to investigate the possibilities implemented by virtual reality in the case of an exhibition for pathological gamers to create a desire to play and work with the patient in an environment identical to the ecological one. Two hypotheses were proposed. On the one hand, the virtual reality exhibition will help to change the desire to play in relation to the game. On the other hand, virtual exhibition sessions associated with cognitive restructuring will have a greater impact on the perception of reality.MethodAfter a diagnosis was made, participation in the study was offered to patients (n = 10) in routine care and able to participate (exclusion criteria). It consisted of four virtual reality exposure sessions integrated with traditional care. Exposure did not exceed 20 minutes. To carry out this study we used the virtual reality headset “Oculus Rift CV1” and the headphones measuring EEG waves, “Emotiv Epoc”. A battery of questionnaires were proposed to evaluate gambling-related behaviors (ICJP, GRCS, UPPS), to analyze the interest of the virtual reality exhibition (SIS, CGI, TEI, EVA), and to glimpse the immersion abilities (QEP and QPI).ResultsTen participants aged 25 to 60 agreed to participate in the study. The results of this study demonstrated the viability of RV gamers’ exposure as a tool that can help reduce pathological gambling symptoms and the severity perceived by therapists (CPI: t = 1.6, P = 0.001; CGI: t = 4.87, P = 0.001) between the beginning of the care and the end of the care and at D+1. We were also able to observe significant results (P < 0.05) concerning a decrease in cognitive distortions (GRCS tot, Illusion of control, Power of prediction, Favorable interpretation).ConclusionThe feasibility study shows that the desire to play is very present during the virtual reality exhibition in accordance with literature studies. The results also demonstrate the utility of virtual reality to allow the patient to elaborate on the cognitive distortions associated with the practice of pathological gambling. From a therapeutic point of view, the results suggest that virtual reality can increase the effectiveness of cognitive restructuring and increase understanding of the urge to play related to stimuli in the environment of play.     

La fragilité de la ;Chair dans la clinique et la psychopathologie de la schizophrénie. Approches de la relation chez Bin Kimura et Erwin Straus

We are trying to study in what way schizophrenia would be a pathology of the Flesh connected with the inability of some patients to Feel. Feeling is a pre-intentional act which cannot be restricted to the simple passivity of receptivity. It is also a noetic act which introduces distance and differentiation between the Self and the Other. This act at the fundament of one's link with the world and the relationships to the others is weakened among the patients suffering from schizophrenia. In reference to Merleau-Ponty, the Flesh refers to the capacity or the incapacity the patient has in keeping with being-in-relation with the Self, the others and the world. As an external space, it refers to the world and as an internal one it refers to the living. One speaks about ‘own body’ or ‘living body’ or Leib, according to Husserl. Flesh and Leib, belong to what is felt before what is thought, to the world of life. This dual link to the living and to the world allows us to compare these two notions to the notion of Aida that we find in Kimura's work. Aida is a virtual space of relationship on the level of the constitution of a Self as well as on the level of the constitution of the world. According to Kimura, schizophrenia is a ‘pathology of Aida’, coming from a failing relation between the Self and the core of life and altering consequently the relationship the patient can have to the others and to the world. It is this essential link at the core of life which, according to Kimura, enables the constitution of the ipseity. But in schizophrenia, this first link does not allow a satisfactory constitution of the Self inducing a disturbed temporality and spatiality. First, the intentionality of consciousness suffers from some distortions; then the modes of spatialization are blending. This confusion between two spaces would be, according to Straus, on the one hand, the beginning of the autistic turning in on the patient's own world or idios cosmos and on the other hand, the beginning of morbid rationalism. These two phenomena lead to losing the Feeling as the mode of relation to the common world or koinos cosmos and consequently a difficulty of being in the Flesh of the world. These phenomena certainly visible with a clinical approach are significantly identifiable with the Rorschach test. On the clinical level, this approach opens onto the setting up of the therapeutic Aida making it possible for the patient to redefine the space and the time which would enable him to be in the field of Feeling and thus in a common space of relation that the therapist brings at the same time as the patient. This is why we will be able to see the specific modes of constitution characterizing the schizophrenic-being and what a proper understanding can bring to the clinical study of schizophrenia.     

Specificity and structure of murine monoclonal antibodies against GM1 ganglioside

Anti-GM1 antibodies have been implicated in the pathogenesis of several neurological diseases, but the role of these antibodies is still controversial. An animal model could provide insight into the mechanisms of these human disorders, but obtaining specific anti-GM1 monoclonal antibodies (mAbs) has been extremely difficult because of the weak immunogenicity of GM1 ganglioside. Four murine mAbs against GM1 were elecited by immunization of mice with lyso GM1 coupled to BSA and GM1 glycolipid. All four IgM,k mAbs bound strongly to GM1, three antibodies (125, 360 and 494) also bound very weakly to asialo GM1 (GA1) and one (156) bound weakly to GD1b. Three antibodies (125, 360 and 494) were encoded by the same V_H and V_K genes. The V_H gene exhibited 97% homology to V_HOX1, a member of the V_HQ52N gene family, the D segment was probably derived from DQ52 and J_H was identical to J_H2. The V_K gene was approximately 99% homologous to V_KRF and J_K was germline J_K2. The V_H gene of mAb 156 exhibited 98% homology to V_H205.12, of the V_HJ558 gene family, the D segement was derived from DFL16.1, and J_H was germline J_H2. The V_K and J_K genes of mAb 156 were identical to V_K8 and J_K1, respectively. The genes encoding these anti-GM1 antibodies were close to germline sequences and have been used to encode other antibodies. This suggests that the unresponsiveness of mice to immunization is probably due to inactivation of self-reactive B cells. These rare anti-GM1 mAbs will be valuable reagents for studies of the pathogenesis of autoimmune neuropathy in animals, and also for analyzing the tissue distribution and functions of GM1.     

An instrument to assess patient satisfaction with epilepsy treatment

AimsPatient satisfaction with antiepileptic drugs is an important component in the management of epilepsy. This study aimed to develop a visual analog scale (VAS) to evaluate patient satisfaction with the effectiveness and tolerability of the current antiepileptic treatment and to identify the most appropriate threshold scores of patient dissatisfaction predictive of a decision to change the antiepileptic drugs.MethodsThis observational study was conducted among patients with epilepsy consulting a neurologist in France. Two anonymous questionnaires were used, one for patients and one for neurologists. The patients' questionnaire assessed satisfaction using a four-point Likert scale and a 10-centimeter VAS. The neurologists' questionnaire evaluated whether the neurologist decided to change the current treatment or not. The determination of the threshold scores predictive of patient dissatisfaction correlated with a change of the medication was performed using analyses of receiver operating characteristic curves. Visual analogue scale scores collected from the patient questionnaire were tested against the responses collected from the neurologist questionnaire.ResultsFive hundred eighteen patient questionnaires and five hundred seven neurologist questionnaires were completed. For the satisfaction with effectiveness and tolerability, the mean VAS scores were 6.7 ± 2.8 and 7.0 ± 2.8, respectively and were, respectively, 6.9 ± 1.7 and 7.0 ± 1.6 for patients who declared to be satisfied with their current antiepileptic drugs and were, respectively, 3.4 ± 1.7 and 3.3 ± 1.9 for those who declared to be dissatisfied. The neurologist decided to change the current antiepileptic drugs in 41.1% (n = 208) of the cases principally because of inadequate effectiveness. With respect to the receiver operating characteristic curves, a VAS threshold of 6 would correctly predict the decision to change the current antiepileptic drugs with sensitivity and specificity values over 73% for both effectiveness and tolerability.ConclusionsThe VAS developed in this study can help patients to evaluate their antiepileptic drugs and to facilitate timely treatment modification when the current treatment is unsatisfactory.     

Development of Exposure to Combat Severity Scale of the Combat Experiences Questionnaire (CEQ)

Combat exposure is detrimental to physical and mental health, and is an important risk factor for Post-traumatic Stress Disorder (PTSD). The current study aimed to develop the first section of a self-report measure (Combat Experiences Questionnaire – CEQ), and to explore its psychometric properties on Portuguese Overseas War Veterans. The Exposure to Combat Severity Scale (CEQ A), assesses the exposure severity to objective scenarios related to military combat, common to contemporary and older theaters of operations. Studies included structural analysis through Rash Model, internal consistency, convergent validity (n = 708), temporal reliability (n = 112) and sensibility to differentiate war Veterans with and without war-related PTSD (N = 40 and N = 47, respectively). The scale's structure presented adequate fit to the data, adequate psychometric properties, and discriminant validity. Thus, the CEQ A is a valid and reliable tool presenting diverse combat scenarios to assess severity of combat exposure in war Veterans.     

Nerve growth factor receptors: analysis of the interaction of ßNGF with membranes of chick embryo dorsal root ganglia

The binding of the β subunit of Nerve Growth Factor (ßNGF) to membrane preparations of 8-day chick embryo dorsal root ganglia (DRG) has been investigated under conditions similar to those used to study the binding of ßNGF to intact single cell dissociates of DRG²³.The equilibrium binding data reveal heterogeneity of binding that is more complex than that seen with intact cells. Binding is not saturable up to¹²⁵IßNGF concentrations of 10⁻⁸ M. Steady-state and kinetic binding data show two sites with dissociation constants similar to those found on DRG cells. In addition, displacement data reveal a binding component with lower affinity (K_d = 10⁻⁶M) which is not found on intact cells.As with intact cells, the difference in the affinities of the two high affinity sites has been shown to be due to different rate constants of dissociation. The kinetics of dissociation of NGF are slower with membranes than with cells, and dissociation characteristics of¹²⁵IßNGF change with increasing time of exposure to membranes. Degradation of¹²⁵IßNGF during incubation with membranes is minimal and does not complicate the analysis of steady-state binding. Insulin does not to either of the two high affinity sites.Heterogeneity of the¹²⁵IßNGF preparation and cooperativity of binding as a cause for the heterogeneity of the binding of NGF has been ruled out. Although there was an apparent increase in the rate of dissociation of¹²⁵IßNGF in the presence of unlabelled NGF, a finding previously interpreted as evidence for negative cooperativity⁷, this was shown to be independent of receptor site occupancy by NGF, and in part due to isotopic dilution within a diffusion barrier around the membranes.     

RANK deletion in neuropeptide Y neurones attenuates oestrogen deficiency‐related bone loss

The RANKL pathway is known to be an important aspect of the pathogenesis of oestrogen deficiency‐induced bone loss. RANK deletion specifically in neuropeptide Y (NPY) neurones has been shown to enhance the ability of the skeleton to match increases in body weight caused by high‐fat diet feeding, likely via the modulation of NPY levels. In the present study, we used ovariectomy in female mice to show that RANK deletion in NPY neurones attenuates bone loss caused by long‐term oestrogen deficiency, particularly in the vertebral compartment. Ovariectomy led to a reduction in NPY expression levels in the arcuate nucleus of NPY^cre/+;RANK^lox/lox mice compared to NPY^cre/+;RANK^lox/+ controls. Because NPY deficient mice also displayed a similar protection against ovariectomy‐induced bone loss, modulation of hypothalamic NPY signalling is the likely mechanism behind the protection from bone loss in the NPY^cre/+;RANK^lox/lox mice.     

Inpatient treatment costs of status epilepticus in adults in Germany

PurposeStatus epilepticus (SE) is an important neurological emergency and a significant source of direct costs related to hospitalization; however, no cost-of-illness (COI) studies have been performed in Europe. The objective of this study was to determine and characterize hospital costs related to the acute inpatient treatment of SE and to provide national estimates of SE hospitalization costs.MethodsAdult inpatient treatment costs related to SE and costs attributable to epilepsy-related hospital admissions were derived from billing data of participating hospitals.ResultsDuring the 4-month study period a total of 96 patients (59.5 ± 21.6 years; 52 male) received inpatient treatment for epilepsy-related reasons, 10 of these (10.4%) were treated for SE. Epilepsy was newly diagnosed in 30/96 patients (31.3%), of whom five presented with SE. The admission costs related to SE (€8347 ± 10,773 per patient per admission) were significantly higher than those related to admissions of patients with newly diagnosed (€1998 ± 1089; p = 0.014) or established epilepsy (€3475 ± 4413; p = 0.026). Of the total inpatient costs (€346,319) 24.4% were attributable to SE, 14.4% to newly diagnosed epilepsy without SE (n = 25) and 61.2% to complications of established epilepsy (n = 61). Extrapolation to the whole of Germany (population 82 million) indicates that SE causes hospital costs of more than €83 million per year while the total of epilepsy-related inpatient treatment costs amounts to €342 million.ConclusionAcute treatment of SE is responsible for a high proportion of hospital costs associated with epilepsy. With a high incidence of SE in the elderly population, the health care systems will face an increasing number of presentations with SE and its associated costs, underlining the necessity to further evaluate the burden and optimize the treatment of SE.