[Acute and chronic toxicities associated with the use and misuse of nitrous oxide: An update]. / Toxicités aiguës et chroniques associées à l'usage et au mésusage du protoxyde d'azote : mise au point.

Nitrous oxide (N2O) is used since the eighteenth century as an anesthetic and analgesic but also for recreational use. If the labelled uses of N2O and their modalities are nowadays perfectly framed, the misuse of N2O takes very alarming proportions among teenagers and young adults. This misuse is the cause of acute (hypoxia, barotrauma, burns, neuropsychiatric disorders) and chronic complications if repeated (myeloneuropathy, anemia, thrombosis, inhalant use disorder). The main mechanism of the latter is mainly related to a functional deficit in vitamin B12 induced by N2O. The management of acute complications is symptomatic. The management of chronic complications is based on vitamin B12 supplementation. The best biomarker of chronic N2O exposure is the elevation of the plasmatic level of methylmalonic acid. In all cases of recreational misuses, addiction treatment is necessary to prevent complications or their worsening by providing information in order to stop consumption.

COgnitive enhancement and consumption of psychoactive Substances among Youth Students (COSYS): a cross-sectional study in France.

OBJECTIVES: This descriptive and analytical study investigated the consumption rates of psychoactive substances among individuals aged 18-25 years in France. More specifically, it enabled assessment of the extent of the neuroenhancement (NE) phenomenon among students in France (including study of the misuse of psychostimulant medicines). STUDY DESIGN: COgnitive enhancement and consumption of psychoactive Substances among Youth Students (COSYS) is a cross-sectional survey of students in France. METHODS: Between January and June 2017, a questionnaire was mailed to students. All questionnaires were completed anonymously and included questions regarding the use of all kind of psychoactive substances, motivations for use and socio-economic situations. Statistics for all variables and the results of a multiple correspondence analysis (MCA) are presented. RESULTS: This study recorded 46,203 respondents, mostly in universities (>60%), mostly women (63.4%), with an average age of 21.4 years. In terms of substance use, medications were cited in the third position after alcohol and tobacco by women (22.48%) and in the fourth position after alcohol, tobacco and cannabis by men (15.14%). Among medications, opiates were the most frequently used, followed by benzodiazepines. Students who declared a non-medical use (NMU) of drugs obtained these through various ways (e.g. family medicine cabinet, a friend, a dealer or via the Internet), or by increasing their recommended doses (e.g. codeine). In total, 18.6% of students consumed psychoactive substances for 'stress management' and 14.1% for 'sleep management'. Results indicated that NE in students is a problem, with 18.6% of students in the COSYS survey confirming the use of psychoactive substances for this reason. There was a very low prevalence for psychostimulant medications (0.57% of men), mostly NMU (67%). MCA yielded three different profiles (doping candidate, experimenter and psychiatric profile) of psychostimulant users, which complicates the implementation of prevention programmes. CONCLUSIONS: It is evident that NMU and 'conventional' use of medications are highly prevalent in French students, especially females. NMU is associated with substance use disorders, psychopathology and suicidality. Social norms and social media increase NMU of psychoactive substances, but also provide a potential platform for anti-NMU campaigns. CLINICAL TRIAL REGISTRATION NUMBER: NCT02954679.

[Cathinones use in Paris]. / Usage de cathinones à Paris.

BACKGROUND: The pattern of recreational drug use has changed over the last decade and now includes a multitude of substances sold as "research chemicals" or new psychoactive substances, "NPS". In France, synthetic cathinones emerged in 2008 (while first mentioned by the French police force in 2007 first alerts among users appeared in 2008) and have grown to be popular drugs of abuse. Under the Official Journal dated 11th June 2010, only mephedrone has been listed as narcotics but "designer drugs" have synthesized new substitute cathinones in order to avoid anti-drug laws. However, since July 2012, in France, all synthetic drugs from the cathinones family have been banned and listed as narcotics following the example of United Kingdom. Despite their recent classification and inclusion on narcotic list, they are readily available on Internet and used widely. Paris Addictovigilance Centre observed a signal of derivate cathinones abuse (21 cases over a two-year period). OBJECTIVE: Paris Addictovigilance Centre and Marmottan Hospital wanted to describe the use of cathinones in the Paris area and alert the health care community about the abuse identification and risk assessment problems of these compounds. After a review of derivated cathinone's chemical structure, pharmacology and toxicology, this article seeks to provide patricians with a clinical description and treatment's modality. RESULTS: Most users of synthetic cathinones will experience euphoria, increased energy, talkativeness, openness and increased sexual arousal. Signs and symptoms of toxicity are consistent with a sympathomimetic toxidrome. The main reasons for care access are psychiatric (hallucinations, psychotic symptoms, agitation) and addiction disorders. Somatic complications were described with various patterns of symptoms such as headache, tachycardia, confusional states, rhabdomyolysis with renal failure or serotonin syndrome. The most important fact is the apparition of the "slam" phenomenon among men who have sex with men (MSM). The "slam" is a compound of three characteristic elements: injection, sexual party and psychostimulant drug. According to users, "slam" is convenient for group sex and is used it to put them into a good mood and a disinhibition state. These compounds cause fast dependence syndrome with strong craving and prolonged psychiatric symptoms and increase infectious risk (HIV, VHC, VHB…). The cathinones family is not detected in conventional urine drug screenings. We point out the lack of confirmatory analytic testing data which remains the only way to determine the actual etiology of the clinical effects observed since drug users do not always know exactly what they took. These substances can be identified by special analyses using gas chromatography or liquid chromatography and mass spectroscopy technology. CONCLUSION: This injection drug is used in order to increase sexual desire, delay orgasm and decrease sexual inhibition and is prevalent in many studies on MSM samples. Cathinones would popularize the "slam". Harm reduction policy requires specific MSM interventions on both sexual and drug addiction networks.

Voriconazole pharmacokinetic variability in cystic fibrosis lung transplant patients.

BACKGROUND: Aspergillosis is a high-risk complication in cystic fibrosis (CF) lung transplant patients. Azole antifungal drugs inhibit CYP3A4, resulting in significant metabolic drug-drug interactions. Voriconazole (VRZ) was marketed without therapeutic drug monitoring (TDM) recommendations, consistent with favorable pharmacokinetics, but regular determinations of plasma VRZ concentration were introduced in our center to manage interactions with calcineurin inhibitors and to document the achievement of therapeutic levels. METHODS: VRZ TDM data analysis for trough concentration (C0) and peak concentration (C2) was carried out, using validated liquid chromatography assay with ultraviolet detection, for 35 CF lung transplant patients (mean age 25 years, mean weight 47 kg, balanced sex ratio) since 2003. Therapeutic range (C0: 1.5 +/- 0.5 - C2 : 4.0 +/- 1.0 mg/L) was expressed relative to pivotal pharmacokinetic trial data. RESULTS: The duration of VRZ treatment ranged from 9 days to 22 months. The recommended standard dose of VRZ (200 mg twice a day, following the loading dose) resulted in significant plasma concentrations (>0.5 mg/L) in 20% of CF lung transplant patients. Therapeutic concentrations were obtained using higher doses (average 570 +/- 160 mg/day, +43%, P<0.01). Despite adaptation, C0 remained <0.5 mg/L (11%), even when the drug was administered intravenously, highlighting the variability of VRZ pharmacokinetics, possibly enhanced by CYP2C19 polymorphism. The risk of inefficacy during periods of underdosage was overcome by treatment with antifungal drug combinations (caspofungin, n=10). The therapeutic index was limited by neurologic effects (14%) and hepatic abnormalities (30%). VRZ concentrations correlated significantly (P<0.01) with aspartate aminotransferase levels but not with bilirubin levels. VRZ acted as a metabolic inhibitor of tacrolimus (C0 to dose ratio 5.8 +/- 2.6, n=31/VRZ versus 1.7 +/- 0.9 alone, P<0.001). Large changes in azole concentration affected the magnitude of the drug-drug interactions and adjustment requirements. CONCLUSIONS: TDM is required because VRZ levels are often undetectable in treated CF lung transplant patients, supporting the use of antifungal drug combinations until achievement of VRZ C0 at a steady state between 1 and 2 mg/L. Plasma VRZ concentrations should be determined for the quantitative, individualized management of drug-drug interactions in lung transplant patients, in particular immunosuppressant such as tacrolimus, considering VRZ to be both a target and an inhibitor of CYP3A4.

Video-thoracoscopic surgical interruption of patent ductus arteriosus. Routine experience in 332 pediatric cases.

OBJECTIVE: Pediatric video-assisted thoracic surgery closure of patent ductus arteriosus can now be performed on a routine basis. We review here our entire experience with this technique. METHODS: Three hundred and thirty two consecutive patients underwent video-assisted closure of patent ductus arteriosus from September 1991 to September 1996. Indications were symptomatic ductus or failure of closure in older children. All complications were carefully noted, as well as intensive care unit stay, and operating room time. RESULTS: Patients were divided in three age groups: less than 6 months (101 patients, 31%), 6-48 months (179 patients, 54%), greater than 48 months (52 patients, 16%). The mean weight was 12.6 kg (range 1.2-65 kg). Associated cardiac anomalies were atrial septal defect (3), ventricular septal defect (5), anomalous pulmonary venous return (1). Six patients had a residual shunt following video-assisted interruption. Five patients had successful immediate clip repositioning (three via video-assisted interruption, two via thoracotomy). One patient continued to have a small shunt, which is followed medically. Complications included recurrent laryngeal nerve dysfunction in six patients (1.8%) (five transient, one persistent). Mean operating time was 20 +/- 1.5 mn and hospital stay averaged 48 h (> 6 months), 72 h (< 6 months). CONCLUSIONS: Interruption of patent ductus can be safely performed by video-assisted technique with minimal morbidity and no mortality. It can be performed in all age group with minimal hospital stay.

Video surgical technique for interruption of patent ductus arteriosus in children and neonates.

Classical surgical interruption of PDA has partially been replaced by trans catheter endovascular closure since 1971. We describe a new technique for PDA closure by video surgery. With the patient under general anesthesia and intubated, two 5 mm holes were made through the left thoracic wall. A video camera and specially devised surgical tools were introduced, such as scissors, dissecting forceps, clip appliers. The ductus was dissected and two titanium clips were applied, completely interrupting the ductus. 282 patients were operated on from April 1991. Mean age was 20 months (range 1 month to 17 years) and mean weight was 13 kg (range 1.2 to 65 kg) Twenty-one had associated lesions not necessitating immediate surgical treatment. All had successful closure of the patent ductus with the video-assisted technique. 6 patients had recurrent laryngeal nerve injury (5 transient, 1 permanent). The usual hospital stay was from 48h to 72h. There were no other complications and no deaths. Video surgery is a rapid, safe and successful technique for closure of the patient ductus arteriosus. The technique is feasible in low-weight and premature infants.

[Closure of patent ductus arteriosus by video thoracoscopy in 282 children]. / Fermeture du canal artériel par vidéo-thoracoscopie chez 282 enfants.

Closure of patent ductus arteriosus by video thoracoscopy is a standardised procedure. The authors report their experience of closure of patent ductus arteriosus by video-thoracoscopy from May 1991 to December 1995. The series included 282 patients divided into 3 groups according to age: under 6 months (78 patients, 27.6%), from 6 months to 4 years (135 patients, 42.88%) and over 4 years of age (69 patients, 24.6%) with an average weight of 12.6 kg (range: 1.2 to 65 kg). Symptomatic pulmonary hypertension was observed in 39 cases and 9 children had associated intracardiac malformations (ostium secundum: 3; ventricular septal defect: 5; abnormal pulmonary venous drainage: 1) which were not corrected. The technique consisted of placing two titanium clips in position under video-thoracoscopy to close the ductus. An echo performed immediately afterwards confirmed closure of the ductus. The main complications were: persistence of a shunt (4 cases) at the beginning of our experience requiring immediate reoperation by video-thoracoscopy in 3 cases and by thoracotomy in one case; left recurrent laryngeal nerve palsy in 6 cases (2.1%) with regression in 5 and persistence in one case; one case of postoperative chylothorax which regressed rapidly. There were no fatalities or haemorrhages and no blood transfusions were required in this series. The average operating time was 20 +/- 15 minutes and the duration of hospital stay around 48 hours when the patients were over 6 months old and 72 hours when less than 6 months of age. Video-thoracoscopic closure of patent ductus arteriosus is rapid, safe, economical, it provides excellent results and may be used in children of all ages.

Video-assisted thoracoscopic surgical interruption: the technique of choice for patent ductus arteriosus. Routine experience in 230 pediatric cases.

Video-assisted thoracoscopic surgical interruption for patient ductus arteriosus is a well-standardized procedure already described. We present our entire series of such cases, from the first case (performed on Sept. 5, 1991) to March 1, 1995. Two hundred thirty patients in a variety of age groups underwent video-assisted interruption: younger than 6 months (70 patients, 30%), 6 to 48 months (123 patients, 54%), and older than 48 months (37 patients, 16%). The mean weight was 12.6 kg (range 1.2 to 65 kg). Thirty-nine patients had symptomatic pulmonary hypertension. Associated intracardiac anomalies included atrial septal defect (three), ventricular septal defect (five), and anomalous pulmonary venous return (one). All patients underwent video-assisted interruption of the patient ductus arteriosus with two titanium clips. Closure was evaluated by postoperative echocardiography before extubation. Five patients had a persistent patent ductus after video-assisted interruption, all early in our experience and related to insufficient dissection resulting in inadequate clip placement. Four patients had successful immediate clip repositioning (three by video-assisted interruption and one by thoracotomy). Subsequent echocardiography revealed persistent closure in these patients. A persistent patent ductus arteriosus with minimal flow was discovered in one patient without symptoms after discharge. Recurrent laryngeal nerve dysfunction was noted in six patients (2.6%, five transient and one persistent). There were no deaths, hemorrhages, transfusions required, or chylothoraces in this series. Mean operative time was 20 +/- 15 minutes, and hospital stay averaged 48 hours for patients younger than 6 months and 72 hours for patients older than 6 months. This is a safe, rapid, cost-effective technique that results in excellent results and a shortened hospital stay. Video-assisted interruption represents the technique of choice for closure of a patient ductus arteriosus.

[Proposition of a new classification of the phylum of the protozoa Ciliophora Doflein, 1901]. / Proposition d'une nouvelle classification du phylum des protozoaires Ciliophora Doflein, 1901.

It is proposed to use all the presently available molecular, ultrastructural, biological and ecological data on ciliates for the new classification of this group of protists. On the basis of the cortical organization and the mode of cilia anchoring as well as the degree of conservation of the cortical pattern during the process of morphogenesis, eleven classes (Karyorelictea, Heterotrichea, Hypotrichea, Oligotrichea, Plagiopylea, Colpodea, Litostomatea, Vestibuliferea, Phyllopharyngea, Nassophorea and Oligohymenophorea) have been distinguished. These classes, in turn, were, according to the "shell theory" of Fleury and coworkers (1992), grouped into three subphyla: Tubulicorticata (presence of the cortical microtubular lattices), Filicorticata (characteristic ecto-endoplasmic microfibrillar boundary) and Epiplasmata (presence of a sub-membraneous epiplasmic layer).

A new video-assisted thoracoscopic surgical technique for interruption of patient ductus arteriosus in infants and children.

Classic surgical interruption of patent ductus arteriosus was partially replaced by transcatheter endovascular closure in 1971. We describe a new technique for ductus closure by video-assisted thoracoscopic surgical interruption, derived from video-assisted endoscopic surgery. With the patient under general anesthesia and intubated, two 5 mm holes were made through the left thoracic wall. A video camera and specially devised surgical tools were introduced; such as scissors, dissectors, and clip appliers. The ductus was dissected, and two titanium clips were applied, completely interrupting the ductus. Thirty-eight patients were operated on from April 1991 to April 1992. Mean age was 23.3 months (range 1.5 to 90 months) and mean weight was 9.5 kg (range 2.4 to 25 kg). Six had associated lesions not necessitating immediate surgical treatment. All had successful closure of the patent ductus with the video-assisted technique, but two needed two such procedures, one because of incomplete immediate ductus closure and one because of partial opening of the clip after 24 hours. One patient had recurrent laryngeal nerve injury and four had pneumothorax on the left side. The usual hospital stay was 2 or 3 days. There were no other complications and no deaths. Video-assisted thoracoscopic surgical interruption was a rapid, safe, and successful technique for closure of the patent ductus arteriosus. Better dissection of the ductus decreased the risk of recurrent laryngeal nerve injury and that of clip opening. In the last 26 patients, in whom a 2 mm multiperforated catheter was used for chest drainage during the first hours, no pneumothoraces occurred. Video-assisted thoracoscopic interruption of the patent ductus arteriosus is feasible in low-weight infants, whereas transcatheter endovascular closure of the ductus usually is not possible. The technique will be applied to premature infants with new instruments designed for the size of these patients.

[Prenatal cardiology: can we treat the fetal heart?]. / Cardiologie prénatale: peut-on traiter le coeur du foetus?

Antenatal diagnosis of heart disease has become very efficient with the advances in ultrasound technology. Accordingly, antenatal treatment of some heart diseases is possible and this is mainly represented by fetal tachycardia and brachycardia. In fetal tachycardia, medical treatment leads to improvement or total curve in approximately 85% of cases. In contrast, there is no efficient medical treatment for fetal bradycardias. In any case, fetal therapy must fulfill several conditions, namely: transplacental transfer of the drug, innocuity for the mother and the fetus, absence of teratogenic effect and low extracardiac tissular accumulation.

[Ventriculo-arterial malpositions with ventricular septal defect. Surgical indications]. / Les malpositions ventriculo-artérielles avec communication interventriculaire. Indications chirurgicales.

Cardiac anomalies with ventriculo-arterial malposition are defined as malformations in which the aortic and/or pulmonary rings are in abnormal relation with the atrioventricular rings. When a high ventricular septal defect is also present, resection of the conal septum enables the reconstitution of normal or close to normal anatomy, without tubal interposition. Experience based upon 188 operations leads us to suggest surgical indications based upon the positions of the aortic and pulmonary rings in relation to the atrioventricular valves. Creation of the left ventricle-aorta channel may require widening of a tight ventricular septal defect, or result in resection or tilting of the conal septum onto which the tricuspid is inserted. Otherwise, left ventricle-aorta passage will be made impossible by the interposition of a straddling mitral or of tricuspid insertions which come to be inserted around the aortic ring. If the pulmonary ring is in a high, normal, position, it will not interfere with fashioning of the left channel. If situated too low, it must be shifted and reimplanted on the right ventricle. Creation of the right ventricle-pulmonary artery channel depends upon the presence or absence of concomitant pulmonary artery hypertension. In the presence of pulmonary artery hypertension, devalvulation and hence pulmonary reimplantation is poorly tolerated and is therefore contraindicated. If the pulmonary ring is in a high position (tricuspid-pulmonary distance of one normal aortic diameter for the child or more), partitioning without pulmonary displacement is the best solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary report: extracorporeal lung support for neonatal acute respiratory failure.

A technique for ventilatory support of life-threatening neonatal acute respiratory failure by use of apnoeic oxygenation and low-frequency positive-pressure ventilation, with extracorporeal membrane CO2 removal through a single-cannula perfusion circuit, is described. 20 severely ill babies with respiratory failure were treated with this technique, 17 of whom survived with no clinical evidence of pulmonary handicap or neurological deficit at discharge from hospital. All 10 patients followed up at 6 months showed normal growth and development.

[Esophageal pacing in children. 38 consecutive cases]. / La stimulation oesophagienne chez l'enfant. A propos de 38 cas consécutifs.

On the occasion of a preliminary series of 38 cases, the authors review the esophageal pacing technique and its main indications. On the therapeutic level, the esophageal lead may be successfully used to decrease supraventricular tachycardias due to reentry (typical or atypical flutter, reciprocating nodal tachycardia with or without WPW). As a means of investigation, esophageal pacing is overall useful to diagnose undocumented paroxysmal tachycardia fits (palpitations), to evaluate the refractory stage of an accessory pathway (WPW) or to assess the refractory stage of antiarrhythmia medications. This investigation may also be used to assess the sinusal function, the atrioventricular conduction (Wenckebach point) and the spontaneous rhythm of atrioventricular blocks after pacemaker insertion. Due to the technical improvements achieved, esophageal pacing may be used presently in pediatric units taking care of children with arrhythmias.

Mediastinal infection after cardiac operation. A simple closed technique.

From March 1984 to March 1987, a simple closed method, previously described for the treatment of osteomyelitis after orthopedic operations, was used to treat deep sternal infection in 11 patients. The basis of this technique is, after meticulous débridement of the wound, to drain all the infected areas with small catheters connected to a bottle inside of which a strong (700 mm Hg) negative pressure is created (Redon drainage device). The method does not require irrigation. The maximum duration of the drainage was 24 days and complete recovery was obtained in all patients without further surgical treatments. The comfort of the patients was optimal.