Schizophrenia following new-onset refractory status epilepticus secondary to antiphospholipid syndrome

New-onset refractory status epilepticus (NORSE) is a drug-resistant status epilepticus that often has a catastrophic outcome. Our patient was diagnosed with NORSE and had an EEG reading that showed status epilepticus persisting for 8 months in general anesthesia. After autoimmune workup showed positive antiphospholipid antibodies, his seizure was controlled, and he was discharged with good condition apart from moderate cognitive impairment. However, he later developed schizophrenia. Although psychiatric disorders have been associated with antiphospholipid syndrome, to the best of our knowledge, it has not been reported to be associated with status epilepticus. We recommend vigilance of psychological complications of refractory status epilepticus’ patients for early psychiatric referral, diagnosis, and treatment.

New-onset refractory status epilepticus (NORSE) is a syndrome of new-onset drug-resistant status epilepticus that often has a catastrophic outcome. Epilepsy is usually associated with psychiatric disorders of different manifestations of which psychosis is an example.1 However, not much is found in the literature review regarding psychiatric disorders following NORSE although a recent study concluded 32% of NORSE patients ended up with altered behavioral states like aggression.2 Schizophrenia following NORSE like in the rare presentation of this case has not been reported in the literature review before, although an association between schizophrenia and autoimmune disorders like APS has been reported.3     

Application of simulated annealing for estimating BAEPs in endocochlear pathologies

In this paper, we propose a new approach aimed at handling the temporal Brainstem Auditory Evoked Potentials (BAEPs) non-stationarity. It is pointed out that for some endocochlear pathologies, BAEPs could be randomly delayed from one response to another. This non-stationarity leads to smoothed BAEPs when applying ensemble averaging or any other technique based on BAEPs stationarity. In that case, waves identification is very difficult, sometimes impossible. The problem consists in estimating time delays. Knowing the distribution of delays allows subsequent study of the dynamic of the cochlea and, perhaps, identification of the nature of its pathology. The approach suggested in this paper is based on Simulated Annealing, used to minimize a non-linear criterion involving delays. This technique is advantageously compared to the non-corrected ensemble averaging method, using a set of simulated data based on a realistic model. As an illustration, results based on real signals recorded from two patients are presented and discussed at the end of the paper.     

Model systems to study the parameters determining the success of phage antibody selections on complex antigens

Phage antibody display technology offers a powerful tool for the isolation of specific antibodies to defined target antigens. Most selection strategies described to date have relied on the availability of purified and often recombinant antigen, providing the possibility to perform selections on a well-defined antigen source. However, when the target antigen cannot be purified (e.g., an integral membrane protein), or if the antigen is unknown (e.g., when searching for novel markers on cells or tissues), panning of phage antibody libraries has to be performed on complex antigen sources such as cell surfaces or tissue sections, or even by in vivo selection methods. This provides a series of technical and experimental challenges. One focus of our research is to select antibodies directed to novel cancer-induced antigens expressed by tumours and by the tumour vasculature. To understand the parameters governing selection on complex antigen sources and to assess the efficiency of these phage library selections, we have set up two model selection systems in which both tumour cells and vascular endothelial cells serve as target "antigen". We describe a model based on phage antibodies directed to the tumour antigen epithelial glycoprotein-2, to compare phage antibody selections on a range of different antigen sources including purified and recombinant antigen, whole live cells, tissue cryosections and in vivo grown solid tumours. Secondly, we describe a model based on a phage antibody directed against the endothelial cell inducible adhesion molecule E-selectin. We compare selections on cultured cell monolayers with selections on cell suspensions immobilised on columns, to determine which selection approach is most suitable for the identification of novel tumour endothelial cell markers. Our data provide insight into the efficiency and thus potency of different selection strategies and show that there are very large differences in the recovery and enrichment of binding phage between the different methods tested. Our results further demonstrate the feasibility of phage antibody selections on whole, intact cells and show that these may sometimes compare favourably to selections on purified antigen. Selections on endothelial cells immobilised on columns compare favourably with selections on cell-monolayers; the most favourable conditions for both selection procedures are described. The implications of our data for phage antibody selections on these different complex antigen sources using either non-immune or immune phage antibody repertoires are discussed. The use of model systems such as the ones described here will help to determine optimal experimental conditions for phage library selections on complex antigens and aid in developing more powerful selection procedures for target discovery.     

Sister chromatid exchanges in patients with retinoblastoma

Spontaneous and mitomycin C(MMC)-induced sisyer chromatid exchanges were studied in 11 patients with retinoblastoma and 7 normal controls. Spontaneous rates were similar in patients and in controls. The MMC-induced rate was found to be significantly higher in bilaterally affected patients than in controls. It is suggested that this increase may be due to a DNA repair deficiency. However, it is not possible to clarify wether this abnormality is associated with the retinoblastoma gene or with another factor acting on the degree of expressivity of the disease in gene carriers.     

Synaptic connectivity of serotonin graft efferents in the suprachiasmatic and supraoptic nuclei of the hypothalamus

We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo-or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions.     

Dual effect of temperature on the human epithelial Na+ channel

The amiloride-sensitive epithelial sodium channel (ENaC) is the rate-limiting step for sodium reabsorption in the distal segments of the nephron, in the colon and in the airways. Its activity is regulated by intracellular and extracellular factors but the mechanisms of this regulation are not yet completely understood. Recently, we have shown that the fast regulation of ENaC by the extracellular [Na⁺], a phenomenon termed self-inhibition, is temperature dependent. In the present study we examined the effects of temperature on the single-channel properties of ENaC. Single-channel recordings from excised patches showed that the channel open probability (P _o, estimated from the number of open channels N·P _o, where N is the total number of channels) increased on average two- to threefold while the single-channel conductance decreased by about half when the temperature of the perfusion solution was lowered from ~30 to ~15 °C. The effects of temperature on the single-channel conductance and P _o explain the changes of the macroscopic current that can be observed upon temperature changes and, in particular, the paradoxical effect of temperature on the current carried by ENaC.     

Multiscale structure of sheet nacre

This work was conducted on Pinctada maxima nacre (mother of pearl) in order to understand its multiscale ordering and the role of the organic matrix in its structure. Intermittent-contact atomic force microscopy with phase detection imaging reveals a nanostructure within the tablet. A continuous organic framework divides each tablet into nanograins. Their shape is supposed to be flat with a mean extension of 45nm. TEM performed in the darkfield mode evidences that at least part of the intracrystalline matrix is crystallized and responds like a 'single crystal'. The tablet is a 'hybrid composite'. The organic matrix is continuous. The mineral phase is thus finely divided still behaving as a single crystal. It is proposed that each tablet results from the coherent aggregation of nanograins keeping strictly the same crystallographic orientation thanks to a hetero-epitaxy mechanism. Finally, high-resolution TEM performed on bridges from one tablet to the next, in the overlying row, did not permit to evidence a mineral lattice but crystallized organic bridges. The same organic bridges were evidenced by SEM in the interlaminar sequence.