Noradrenergic α1, α2, and ß1receptors mediate VNS-induced theta oscillations.

Although vagal nerve stimulation (VNS) has been employed with success for almost four decades in many central nervous system disturbances, the physiological and pharmacological processes underlying this therapy are still unclear. Searching for central mechanisms of VNS is clinically limited. Hence, in many experiments, VNS technique is tested on the model of laboratory animals. In the present study we proceed with the experiments to verify some central effects of VNS. Specifically, we focussed on the hippocampal formation (HPC) noradrenergic profile which underlines the VNS-induced theta oscillations in anesthetized rats (Broncel et al., 2017; 2021). The effects of noradrenaline (NE) and selective noradrenergic α and ß agonists and antagonists were tested in experiments organized in three stages. Initially, a nonspecific noradrenergic agonist, noradrenaline, was administrated. In the second stage, noradrenergic α and ß agonists were applied. In the last stage, the administration of selected agonists was pretreated by specific antagonists. The results of the present study provide evidence that the selective activation of HPC α1, α2, and ß1 noradrenergic receptors produce the inhibition of VNS-induced theta oscillations. Hippocampal ß2 and ß3 receptors were found not to be involved in the modulation of oscillations produced by the vagal nerve stimulation. The obtained outcomes are discussed in light of the effects of increased exogenous NE and induced release of endogenous NE.

Noradrenergic Profile of Hippocampal Formation Theta Rhythm in Anaesthetized Rats.

The present study was undertaken to identify the noradrenergic receptors underlying the production of hippocampal formation (HPC) type 2 theta rhythm. The experiments were performed on urethanized rats wherein type 2 theta is the only rhythm present. In three independent stages of experiments, the effects of noradrenaline (NE) and selective noradrenergic α and ß agonists and antagonists were tested. We indicate that the selective activation of three HPC noradrenergic receptors, α1, α2 and ß1, induced a similar effect (i.e., inhibition) on type 2 theta rhythm. The remaining HPC ß2 and ß3 noradrenergic receptors do not seem to be directly involved in the pharmacological mechanism responsible for the suppression of theta rhythm in anaesthetized rats. Obtained results provide evidence for the suppressant effect of exogenous NE on HPC type 2 theta rhythm and show the crucial role of α1, α2 and ß1 noradrenergic receptors in the modulation of HPC mechanisms of oscillations and synchrony. This finding is in contrast to the effects of endogenous NE produced by electrical stimulation of the locus coeruleus (LC) and procaine injection into the LC (Broncel et al., 2020).

Effects of locus coeruleus activation and inactivation on hippocampal formation theta rhythm in anesthetized rats.

Previously obtained data suggests that noradrenaline (NE) released from the efferent locus coeruleus (LC) endings in hippocampal formation (HPC) may serve as an important modulating signal involved in the pharmacological mechanisms responsible for the production of type 2 theta rhythm in rats. Hence, two distinct hypotheses were tested in the present study: 1/ if the decrease in HPC level of NE is correlated with the desynchronization of HPC field potential, then the inhibition of LC would be expected to abolish HPC type 2 theta rhythm; 2/ if the increase in HPC NE level is correlated with synchronization of HPC field potential, then the stimulation of LC would be expected to produce type 2 theta. The experiments were performed using an experimental model of HPC type 2 theta rhythm recorded in urethanized rats. It was demonstrated that electrical stimulation of LC produced type 2 theta rhythm whereas procaine injection into LC, in contrast, reversibly abolished type 2 theta. The possible relation of type 2 theta rhythm with some disturbances of Alzheimer disease are addressed.

Vagal nerve stimulation as a promising tool in the improvement of cognitive disorders.

Vagal nerve stimulation (VNS) is known as an effective method of treatment in a number of neurological disorders. The low risk of side effects also makes it useful in clinical trials in other diseases. Branches of the vagal nerve innervate the anatomical structures known to be involved in memory processing. That is why it seems justified that several studies emphasize the impact of VNS on the cognitive and memory function in both healthy volunteers and patients with epilepsy and Alzheimer's disease. Results have shown that VNS can modulate different types of memory depending the protocol of stimulation in non-demented patients after both short term and chronic VNS application. Transcutaneous vagal nerve stimulation (tVNS), which is a non-invasive method of VNS, opens up new perspectives for different clinical applications.

[Autoimmune hemolytic anemia and immune thrombocytopenia associated with Hodgkin disease: Retrospective monocentric study]. / Cytopénies auto-immunes associées au lymphome de Hodgkin : étude rétrospective monocentrique.

INTRODUCTION: Hodgkin's lymphoma (HL) is less common than non-Hodgkin lymphoma and is rarely associated with autoimmune cytopenia. METHOD: We report a consecutive, monocentric and retrospective series of HL patients diagnosed with concomitant or subsequent autoimmune cytopenia over a period of 8 years. RESULTS: We report 4 out of 84 HL patients (4.8%) diagnosed with autoimmune cytopenia (4 immune thrombocytopenia including 2 Evans' syndromes). They were 4 males (average age 24 years for the 3 youngest, and one over 60 years old). Autoimmune cytopenia revealed lymphoma in 2 patients and occurred after HL treatment in the two other patients (5 and 36 months from the end of chemotherapy) without HL relapse. All cytopenias were resistant to conventional treatments (glucocorticoids, intravenous immune globulin, rituximab) and sensitive to chemotherapy when indicated for HL treatment. CONCLUSION: In our series, the predominance of males, a higher frequency of immune thrombocytopenia than autoimmune hemolytic anemia, the resistance to usual treatments and the efficacy of specific chemotherapy were consistent with the literature. Unexpectedly, patients were young and with nodular sclerosis morphology (vs. mixed cellularity) in 3 of 4 cases.

Peripherally inserted central catheter placement in patients with coagulation disorders: A retrospective analysis.

OBJECTIVE: To assess the safety of peripherally inserted central venous catheter (PICC) placement in patients with altered and uncorrected coagulation parameters or receiving antiplatelet therapy. MATERIALS AND METHODS: Medical charts of all patients with major primary and secondary hemostasis disorders, combined hemostasis disorders or on antiplatelet therapy and who had undergone non-tunneled PICC placement from December 2009 to December 2013, were retrospectively reviewed. A hemostatic disorder was defined as a platelet count (PC)≤50×10(9)/L, an international normalized ratio (INR) ≥ 2, or an activated partial thromboplastin time (aPTT)≥66s, alone or in combination. Underlying hemostasis disorders were not corrected and antiplatelet therapy was not interrupted before PICC placement in any patient. 4, and 5-Fr single and dual lumen PICCs were used. RESULTS: A total of 378 PICCs were placed in 271 patients (180 men and 91 women; mean age=62±13.4years; range, 18-93 years)) with coagulation disorders. Eighty-nine (23%) PICCs were placed in patients who were receiving antiplatelet therapy (aspirin, clopidogrel, rivaroxaban). Thrombocytopenia was noted in 269PICC placements (71%). Among these patients, 23 had disseminated intravascular coagulation. Prolonged INR and aPTT were observed in 42 procedures (11.1%). PICC placement was achieved in all patients, with a mean number of 1.14 attempts. Peripheral venous access was obtained through the basilic and the brachial vein respectively in 295 (79.1%) and 83 (20.9%) of patients. The placements were performed by residents and fellows in 108 (28.5%) and 270 (71.5%) procedures, respectively. No early or late complications were reported after any procedure. No accidental puncture of the brachial artery occurred. CONCLUSION: In patients with severe primary and secondary hemostasis disorders, combined hemostasis disorders or on antiplatelet therapy, PICC placement is a feasible and safe procedure and does not require correction of coagulation parameters or discontinuation of antiplatelet therapy.

An 8-year survey of strains identified in blood cultures in a clinical haematology unit.

The aim of our study was to determine the epidemiological profile and the antibiotic susceptibility of bacteria and fungi identified from blood cultures in the patients of the clinical haematology unit. A retrospective study was carried out over an 8-year period (2003-2010) in the clinical haematology unit of the Percy Military Medical Center. During this period, we collected 723 isolates: Gram-negative bacilli (70.8%) and Gram-positive cocci (18.7%). The four most commonly isolated species were Escherichia coli (18.5%), Pseudomonas aeruginosa (14.8%), Stenotrophomonas maltophilia (6.2%) and Staphylococcus epidermidis (5.4%). The rate of methicillin-resistant Staphylococcus aureus was 6.45% and that of coagulase-negative staphylococci 61.2%. No resistance to glycopeptides was observed. In E. coli, as in the Klebsiella-Enterobacter-Serratia group, a 27% resistance to fluoroquinolones was observed. Concerning P. aeruginosa, the phenotypes were distributed over penicillinase (23.4%) and cephalosporinase (13.1% were resistant to ceftazidime). The impermeability rate of imipenem was 9.3%. The aggressiveness and duration of haematological treatments explains why infections remain one of the main complications of neutropenia. The emergence of new or unusual bacteria is highly likely. Antibiotic selective pressure and long periods of hospitalization could explain the emergence of multiresistant bacteria. As a consequence, epidemiological surveillance is indispensable.

Fractionated doses of gemtuzumab ozogamicin combined with 3 + 7 induction chemotherapy as salvage treatment for young patients with acute myeloid leukemia in first relapse.

Current salvage therapies for relapsed acute myeloid leukemia (AML) are unsatisfactory. We retrospectively evaluated the efficacy and toxicity of fractionated doses of gemtuzumab ozogamicin (GO) combined with a standard 3 + 7 induction regimen in young patients with AML in first relapse. Salvage regimen consisted of GO 3 mg/m² on days 1, 4, and 7; cytarabine, 200 mg/m² on days 1-7; and daunorubicine, 60 mg/m²; or idarubicine, 12 mg/m² on days 1-3. Fourteen patients were treated between April 2008 and April 2011. Median age was 46 years (29-58), median white blood cell count is 3.4 109/L (0.9-19), and median first complete remission (CR) duration is 11 months (1-42). All the patients had previously received high or intermediate doses of cytarabine as consolidation therapy. Salvage treatment was performed as scheduled for the 14 patients, using daunorubicine in 12 patients and idarubicine in two. Overall response rate was 79 % with six CR and five CR with incomplete platelet recovery. Median times to neutrophil (>0.5 109/L) and platelet (>20 109/L) recovery were 29 days (23-32) and 36 days (28-48), respectively. Allogeneic transplantation was performed in the 11 responding patients within a median time of 4 months (3-10). Three mild and one moderate veno-occlusive disease (VOD) occurred after salvage and two moderate VOD after transplantation. Median and 2-year overall survival (OS) were 10 months and 42 %, respectively. For responders, estimated 2-year OS was 53 % (median OS not reached). This salvage regimen seems safe and effective in younger patients with AML in first relapse allowing allogeneic transplantation in CR2 for most patients.

[Evans syndrome: be careful of over-diagnosis]. / Syndrome d'Evans: attention aux diagnostics par excès.

INTRODUCTION: Evans syndrome (ES) is characterized by the coexistence of an autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Despite being frequently evocated in the simultaneous presence of anemia and thrombocytopenia, this rare disease only accounts for 0.8 to 3.7% of patients with ITP or AIHA. CASE REPORTS: We report three suspected cases of ES, diagnosed in the presence of thrombocytopenia and hemolytic anemia association, with a positive direct Coombs test in two patients. Standard ES treatment failure and occurrence of additional features subsequently led to correct diagnosis to thrombotic thrombocytopenic purpura, myelodysplastic syndrome with AIHA, and ITP with hemorrhagic anemia, respectively. CONCLUSION: Bicytopenias, even in an immunological context, are not sufficient to ascertain ES diagnosis. Our cases illustrate the diagnostic difficulties that may arise in daily practice, and induce over-diagnosis of this rare disease.

[Periprocedural management of hemostasis risk in interventional radiology]. / Prise en charge du risque hémostatique au cours des actes de radiologie interventionnelle.

Given the increasing demand for interventional image-guided procedures, radiologists are increasingly sollicited by clinicians to participate in the management of patients prior to and after the interventional procedure, especially with regards to hemostasis. Therefore, radiologists should be familiar with the risk of procedure related hemorrhage. Based on consensus guidelines published by the Society of Interventional Radiology (SIR), the risk of hemorrhage for each interventional procedure will be classified. Recommendations for preprocedure testing based on the type of procedure planned will be reviewed. Finally, limitations of hemostasis parameters will be discussed along with management of anticoagulants and antiplatelet agents before the procedure.

[Usefulness of JAK2 mutation assessment in recurrent deep venous thrombosis]. / La recherche de la mutation JAK2 peut-elle être utile dans le bilan étiologique d'une maladie thromboembolique récidivante ?

The search of JAK2 V617F mutation is a useful tool for the diagnosis of myeloproliferative disorders (MPD). This case report highlights the potential usefulness of this testing in recurrent deep venous thrombosis (DVT) of lower limb. We report a 73-year-old man who presented with three spontaneous episodes of lower limb DVT. The third episode occured while he was receiving fluindione. MPD was suspected because of an increased hematocrit (55 %) and hemoglobin (17g/dl) level. Red cell blood volume was increased and a JAK2 V617F mutation was detected confirming the diagnosis of polycythemia vera. The usefulness of JAK2 mutation for the diagnosis of MPD has been widely demonstrated. Also, some studies confirmed its usefulness in apparently idiopathic abdominal venous thrombosis. This report highlights the possible interest of JAK2 mutation in unexplained recurrent lower limb DVT, especially when it occurs under anticoagulant therapy.

Which role for rituximab in hairy cell leukemia? Reflections on six cases.

Hairy cell leukemia (HCL) is a rare, chronic, B-cell, lymphoproliferative disorder. Treatment has been revolutionized by the advent of interferon (IFN)-alpha and purine analogs (PA). First-line therapy with PA yields complete response rates of 75-100%, with many long-lasting remissions. In the event of profound neutropenia and/or infectious complications, a short sequence of IFN-alpha may precede PA treatment. Because of the excellent results achieved with PA therapy, the potential role of rituximab (an anti-CD20 monoclonal antibody that is highly effective against most B-cell lymphomas) in HCL has yet to be elucidated. Six HCL cases treated with rituximab are reported herein with a view to elucidating the potential role of the drug in HCL. The indications essentially consist of relapsing or refractory disease, avoiding the cumulative toxicity of PA, consolidation therapy in order to eradicate minimal residual disease, and first-line therapy for patients with contraindications to PA and IFN-alpha.

[Hematological disorders and hypereosinophilias]. / Hyperéosinophilies et affections hématologiques.

Hematological disorders are the third cause of hypereosinophilia, after allergic and parasitic diseases. Hematological disorders associated with hypereosinophilias can be classified as clonal, reactive or idiopathic, and recently the improvements of cytogenetic, molecular biology and immunology have allowed to revisit numerous cases previously diagnosed as idiopathic hypereosinophilic syndrome. Reactive eosinophilias are mainly associated with lymphoma or abnormal, often clonal T lymphoid population. Clonal eosinophilia is related either to various myeloid malignancies or to a genuine myeloproliferative disorder from the eosinophile lineage, the so-called chronic eosinophilic leukaemia. Chronic eosinophilic leukaemia can be associated with recurrent genes rearrangements involving PDGFRA, PDGFRB and FGFR1 or with clonal abnormalities not yet categorized. Idiopathic hypereosinophilic syndrome remains an exclusive diagnosis in presence of moderate or severe unexplained eosinophilia with target organ damage. The purpose of the diagnostic work-up of hypereosinophilic syndrome is to evidence either an abnormal T cell population or a clonal haematopoiesis. Imatinib mesylate dramatically improves chronic eosinophilic leukaemias associated with PDGFR abnormalities, while corticosteroids are still the main treatment for the other patients. In a near future, advances could arise from identification of new genes involved in clonal eosinophilia or in alternative therapy such as the anti-IL-5 antibodies.

Effect of posterior hypothalamic injection of procaine on the hippocampal theta rhythm in freely moving cats.

Earlier in vivo studies conducted on freely moving and anesthetized rats demonstrated that the posterior hypothalamus (PH) comprises pathways critical for producing the synchronous hippocampal formation (HPC) theta rhythm. In addition, these findings suggested that the frequency of the HPC theta was encoded in the PH and then was fed via the medial forebrain bundle to the medial septum and HPC. In the present study we attempted to verify this hypothesis with use of a different in vivo model--freely moving cats. The microinjection of the local anaesthetic, procaine, into the PH region reversibly suppressed the spontaneous as well as sensory and electrically induced HPC theta. However, in contrast to rats, in freely moving cats microinjection of procaine into the PH reduced the amplitude of the HPC theta but had no effect on theta frequency. We conclude that in freely moving cats the PH region comprises a critical part of the ascending brainstem pathway, for production of the HPC theta rhythm. In contrast to rats, in freely moving cats ascending inputs from the brainstem to the PH contribute mainly to the amplitude of the HPC theta rhythm.

Window effect of temperature on carbachol-induced theta-like activity recorded in hippocampal formation in vitro.

The effect of different temperatures of ACSF (18-42 degrees C) on carbachol (CCH)-induced field potentials were examined in the present study. Two hundred and thirty one experiments were performed on hippocampal formation slices maintained in a gas-liquid interface chamber. All slices were perfused with 50 microM CCH. A recording electrode was positioned in the region of CA3c pyramidal cells. The experiments gave two main findings. First, in a presence of continuous cholinergic stimulation the temperature of the bathing medium per se determined the rate of synchronization of the field potentials and pattern of EEG activity recorded. Second, within the temperature range from 33 degrees to 37 degrees C a window effect of temperature on CCH-induced theta-like activity (TLA) was noted: in this temperature range all slices tested responded only with one pattern of EEG activity-TLA. The results are discussed in light of temperature effects on hippocampal neuronal networks.

[Basic micro-electrophysiologic techniques used in neurobiology]. / Podstawowe techniki mikroelektrofizjologiczne w neurobiologii.

Problems of application of microelectrophysiological techniques in neurobiology are addressed. Authors focused on five basic recording techniques: micro-EEG, multi unit activity, single unit activity, intracellular recording and patch clamp techniques.

[Use of trans-slice technique for microencephalographic examinations in vitro]. / Zastosowanie techniki skrawków czastkowych w badaniach mikroelektroencefalograficznych in vitro.

The present paper reviews the experimental data concerning the use of trans-slice preparation technique in investigation of theta-like activity generation in the limbic cortex. Specific aspects of the technical arrangement of the hippocampal formation and entorhinal cortex microelectroencephalographic registration were emphasized.