Are the results of electrophysiological study different in patients with a pre-excitation syndrome, with and without syncope?

AIMS: Syncope in Wolff-Parkinson-White (WPW) syndrome may reveal an arrhythmic event or is not WPW syndrome related. The aim of the study is to evaluate the results of electrophysiological study in WPW syndrome according to the presence or not of syncope and the possible causes of syncope. METHODS AND RESULTS: Among 518 consecutive patients with diagnosis of WPW syndrome, 71 patients, mean age 34.5 +/- 17, presented syncope. Transoesophageal electrophysiological study in control state and after isoproterenol infusion was performed in the out-patient clinic. Atrioventricular re-entrant tachycardia (AVRT) was more frequently induced than in asymptomatic patients (n = 38, 53.5%, P < 0.01), less frequently than in those with tachycardia; atrial fibrillation (AF) and/or antidromic tachycardia (ATD) was induced in 28 patients (39%) more frequently (P < 0.05) than in asymptomatic patients or those with tachycardia. The incidence of high-risk form [rapid conduction over accessory pathway (AP) and AF or ATD induction] was higher in syncope group (n = 18, 25%, P < 0.001) than in asymptomatic subjects (8%) or those with tachycardias (7.5%). Maximal rate conducted over AP was similar in patients with and without syncope, and higher in patients with spontaneous AF, but without syncope. Results were not age-related. CONCLUSION: Tachycardia inducibility was higher in patients with syncope than in the asymptomatic group. The incidence of malignant WPW syndrome was higher in patients with syncope than in asymptomatic or symptomatic population, but the maximal rate conducted over AP was not higher and another mechanism could be also implicated in the mechanism of syncope.     

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

Background

Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors.

Design and Methods

We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation.

Results

We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice.

Conclusions

These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment.Key words: human induced pluripotent stem cells, terminal maturation, erythropoietic differentiation     

Effect of cyclosporin A on morphine-induced place conditioning in mice: involvement of nitric oxide

Cyclosporin A is shown to attenuate antinociceptive effects of morphine, development and expression of morphine-induced tolerance and dependency via nitric oxide (NO) pathway. In the present study, the effect of systemic cyclosporin A on morphine-induced conditioned place preference (CPP) and the probable involvement of nitric oxide were assessed in mice. Our data showed that administration of morphine (1, 2.5, 5, 7.5, 10 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. The maximum response was obtained with 5 mg/kg of morphine. Cyclosporin A (5, 10 mg/kg) and N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5, 5, 10 mg/kg), a nonselective nitric oxide synthase (NOS) inhibitor, did not induce either conditioned place preference or conditioned place aversion (CPA), while cyclosporin A (20 mg/kg) induced CPA. Both cyclosporin A (10, 20 mg/kg) and L-NAME (5, 10 mg/kg), in combination with morphine (5 mg/kg) during conditioning, significantly suppressed acquisition of morphine-induced place preference. Lower and per se noneffective doses of Cyclosporin A (1, 2.5, 5 mg/kg) and L-NAME (2.5 mg/kg), when coadministered, exerted a significant potentiating effect on the attenuation of morphine-induced place preference. Aminoguanidine (50, 100 mg/kg), the specific inducible nitric oxide synthase (iNOS) inhibitor, whether alone or in combination with cyclosporin A failed to show this inhibitory effect on morphine-induced place preference. In conclusion, decreasing nitric oxide production through inhibiting constitutive nitric oxide synthase may be a mechanism through which cyclosporin A attenuates morphine-induced place preference.     

Iniencephaly: clinical, radiological and surgical findings

The authors report a case of iniencephaly in a 6-year-old boy with a huge occipital bone defect and encephalocele, extensive spina bifida of the cervical vertebrae and fixed retroflexion of the head due to Sprengel's deformity. He presented with some cerebellar and cranial nerve symptoms and new episodes of neck pain and drop attacks. Brain imaging confirmed progressive deformity of the brain stem, cerebellar herniation into the encephalocele sac and ventriculomegaly. Surgical repair of the encephalocele was performed with preservation of all herniated cerebellar tissue and the release of thick arachnoid adhesions to make more space to return the herniated neural tissue from the sac to the cranium. The patient was found to have progressive facial palsy and intracranial hypertension 3 days after surgery, which improved with ventriculoperitoneal shunting. Iniencephaly is generally a fatal anomaly, and only 7 such patients have been reported to have survived. Because of the fatality of this anomaly, prenatal diagnosis of iniencephly and pregnancy termination are important. The patient presented herein is only the second patient with iniencephaly and encephalocele to be operated on. The severity of associated systemic and cranial abnormalities is fundamental with regard to survival. Essential points for surgery are preparing enough space to save herniated functional neural tissues, management of associated hydrocephalus and brain stem rotation/compression due to decreased postoperative space. In the surviving child, early correction of Sprengel's deformity would provide a better aesthetic position of the neck with preservation of brachial plexus integrity.     

On the In Vivo Deformation of the Mitral Valve Anterior Leaflet: Effects of Annular Geometry and Referential Configuration

Alteration of the native mitral valve (MV) shape has been hypothesized to have a profound effect on the local tissue stress distribution, and is potentially linked to limitations in repair durability. The present study was undertaken to elucidate the relation between MV annular shape and central mitral valve anterior leaflet (MVAL) strain history, using flat annuloplasty in an ovine model. In addition, we report for the first time the presence of residual in vivo leaflet strains. In vivo leaflet deformations were measured using sonocrystal transducers sutured to the MVAL (n = 10), with the 3D positions acquired over the full cardiac cycle. In six animals a flat ring was sutured to the annulus and the transducer positions recorded, while in the remaining four the MV was excised from the exsanguinated heart and the stress-free transducer positions obtained. In the central region of the MVAL the peak stretch values, referenced to the minimum left ventricular pressure (LVP), were 1.10 ± 0.01 and 1.31 ± 0.03 (mean ± standard error) in the circumferential and radial directions, respectively. Following flat ring annuloplasty, the central MVAL contracted 28% circumferentially and elongated 16% radially at minimum LVP, and the circumferential direction was under a negative strain state during the entire cardiac cycle. After valve excision from the exsanguinated heart, the MVAL contracted significantly (18 and 30% in the circumferential and radial directions, respectively), indicating the presence of substantial in vivo residual strains. While the physiological function of the residual strains (and their associated stresses) are at present unknown, accounting for their presence is clearly necessary for accurate computational simulations of MV function. Moreover, we demonstrated that changes in annular geometry dramatically alter valvular functional strains in vivo. As levels of homeostatic strains are related to tissue remodeling and homeostasis, our results suggest that surgically introduced alterations in MV shape could lead to the long term MV mechanobiological and microstructural alterations that could ultimately affect MV repair durability.     

Huge hydrocephalus: definition, management, and complications

Objective  

Lack of comprehensive knowledge and numerous socioeconomic problems may make the parents leave hydrocephalic children untreated, leading to progressive hydrocephalus and eventual unordinary big head. Management of huge hydrocephalus (HH) differs from common hydrocephalus. We present our experience in the management of these children.