Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells.

OBJECTIVES: In obesity, while hyperleptinemia highly correlates with excess fat mass, the status of gastric leptin remains unknown. Here, we investigated the expression of leptin in stomach biopsies of obese humans and analyzed the temporal changes of gastric leptin expression in response to diet-induced obesity and its impact on 5-hydroxytryptamine (5HT)-producing cells. METHODS: Enterochromaffin (EC) cells and expression of leptin, PAX4 (critical factor for EC specification), tryptophane hydroxylase-1 (TPH1, the peripheral rate-limiting enzyme for 5HT) and 5HT were examined by immunofluorescence, quantitative real-time PCR, radioimmunoassay, respectively, in stomach and duodenum biopsies from 19 obese and 14 normo-weighed individuals, and in mucosa scrapings from C57Bl6/J diet-induced obese mice, leptin-deficient ob/ob mice and intestine-specific leptin receptor isoform B-deficient mice. RESULTS: Gastric mucosa of obese subjects displays an increased expression of leptin (LEP mRNA by fivefold and protein by twofold, P<0.01), TPH1 ((1.75-2.73, 95% confidence interval (CI)) vs (0.38-0.67, 95% CI); P<0.01) and PAX4 ((1.33-2.11, 95%CI) vs (0.62-0.81, 95% CI); P<0.01) as compared with normo-weighed individuals. In diet-induced obese mice, the overexpressions of gastric leptin, antral Pax4, Tph1 and increased EC cell number occurred before the onset of obesity and hyperleptinemia (reflect of adipocyte leptin production). In addition, leptin deficiency was associated with reduced Pax4 mRNA, whereas oral leptin treatment enhanced both Tph1 and Pax4 mRNA. Finally, mice with an intestine-specific deletion of leptin signaling exhibit significant decrease in duodenal mucosa 5HT content. CONCLUSIONS: These data demonstrate that gastric leptin is upregulated in obese individuals. RESULTS from high-fat diet mice showed that overexpression of gastric leptin that is linked to gut '5HT pathway' occurred before the onset of obesity and expansion of fat mass. This may be relevant in the pathophysiology of obesity.

Cone Beam-CT-Based Bone Volume Assessments of Alveolar Synthetic Bone Graft GlassBONE™ in Cleft Lip and Palate Patients: A Retrospective Study.

Background: Clefts of the lip and palate (CLP) are facial deformities that require multiple surgical procedures during childhood. One of these steps consists of filling the alveolar space with bone graft, traditionally removed from the iliac crest. However, this procedure could be invasive in children. Aim: Here, we aimed to evaluate the outcomes of GlassBONE™ graft, a bioactive glass used as a bone substitute, as an alternative to the deleterious autologous bone graft in children. Materials & methods: Retrospective monocentric study with 17 children aged 7.5 ± 2.2 yo [3.8-13.3 yo] carrying CLP. This technique has been established at La Timone Children hospital (Assistance Publique - Hôpitaux de Marseille) since 2011. Clinical (scar, graft rejection and periodontal status) and radiological (both panoramic radiographs and cone beam-CT) follow-up was conducted one year after the graft. The primary outcome was the reduction of the cleft volume, and secondary was the eruption of the adjacent tooth through the graft. Results: GlassBONE™ permitted a significant reduction in the cleft volume by 42.4 ± 27.7% [0.6-81.1%] (p < 0.0001), corresponding to a filling of 57.6 ± 27.7% of the alveolar cleft. GlassBONE™ is well tolerated, ensuring satifactory clinical results (improvement in both scar and periodontal coverage), as well as the physiological evolution of the germs through the biomaterial. GlassBONE™ appears particularly suitable for small volumes, and we were able to determine a minimum volume of approximtely 0.259 + / - 0.155 cc required for a successful bone fusion. Conclusion: The bioactive glass GlassBONE™ could be safely used in children with small CLP cases, providing satisfactory clinical and radiological results.

Nation-wide monitoring campaign of 49 biocides and surfactants in surface waters and wastewaters.

Despite their intensive use and their impact on ecosystems, biocides and surfactants are still poorly regulated and poorly monitored at large scale. In the frame of the revision of the national regulatory surveillance plan of surface waters, France planned in 2018 a monitoring campaign at national scale focused on these two types of substances of very emerging concern. Forty-nine contaminants (32 biocides and 17 surfactants) were investigated in surface water and sediment samples from 91 sampling sites, and in effluent and sludge samples of 7 wastewater treatment plants (WWTP), in mainland France and overseas regions. Between 33 and 52 % of the target contaminants were quantified at least once in water and sediment. High frequencies of quantification were observed for the surfactants (up to 91 % in water samples and up to 57 % in sediment samples for LAS C10-C13) and for the biocides (up to 64 % for fipronil in water samples and up to 90 % for methyl nonyl ketone in sediment samples). The median concentrations of surfactants were up to 2 µg/L in mainland surface water samples and up to 528 µg/kg in sediment samples, and for biocides, the median concentrations were up to 0.18 µg/L in mainland surface water samples and up to 104 µg/kg in sediment samples. PNEC exceedances in water and sediment were determined for both types of substances. The analysis of effluent and sludge suggested significant but not total removal of these substances in the WWTP. Temporal and spatial variations of the concentrations of both types of substances in surface water samples were also observed, suggesting both punctual and diffuse contamination sources of the surface water investigated.

The average Adjusted Symptom Score, a new primary efficacy end-point for specific allergen immunotherapy trials.

BACKGROUND: In clinical trials, the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups. OBJECTIVE: To develop and describe the average Adjusted Symptom Score (AdSS), a new end-point reflecting symptom severity and rescue medication use in allergic rhinoconjunctivitis trials. METHODS: To calculate the AdSS, the RTSS is adjusted as follows: if a patient takes rescue medication on day d, the day's AdSS (AdSS(d)) is defined as the value of RTSS(d) or AdSS(d-1), whichever is higher. The AdSS on the following day (AdSS(d+1)) is defined as the value of RTSS(d+1) or AdSS(d), whichever is higher. The average of the daily AdSSs (during the season) was calculated post hoc for two trials investigating the efficacy of five-grass pollen sublingual immunotherapy tablets in adult and paediatric patients and compared with the ARTSS and three other outcome measures (the average Rescue Medication Score (ARMS), the ARTSS and the average Combined Score). RESULTS: The average AdSS clearly discriminated between active and placebo treatments and confirmed the original ARTSS results. Adjustment for rescue medication use decreased the observed placebo effect. CONCLUSION AND CLINICAL RELEVANCE: The average AdSS can be a valuable alternative to the ARTSS as a primary efficacy end-point in grass pollen allergic rhinoconjunctivitis trials. By adjusting the RTSS for rescue medication use, the AdSS can estimate symptom severity and the treatment effect more accurately. The AdSS is now being tested prospectively in large clinical trials.

The allergen challenge chamber: a valuable tool for optimizing the clinical development of pollen immunotherapy.

The clinical development of allergen immunotherapy for allergic rhinoconjunctivitis because of pollen is complicated by seasonal, geographical and subject-related variability in allergen exposure. Using an allergen challenge chamber (ACC), a room that enables reproducible challenges with controlled levels of inhalant allergens for several hours, these factors can be controlled. The ACC has often been used to evaluate symptomatic medications but is underexploited in the field of allergen immunotherapy. When used in conjunction with a programme of natural-exposure trials, the ACC enables researchers to (i) facilitate the allergen immunotherapy dose-finding process, (ii) accelerate the transition from Phase I/II to Phase III trials, (iii) characterize the onset and maintenance of action, (iv) avoid the confounding effects of rescue medication, (v) better characterize the baseline or pretreatment characteristics of trial subjects, (vi) perform better-standardized physical and laboratory measurements during an acute challenge, (vii) simplify trial logistics and use smaller numbers of subjects than would be required in equivalent natural-exposure studies and (viii) support (but not replace) Phase III natural-exposure trials for the investigation into long-term and disease-modifying effects. ACC studies can further increase levels of evidence for allergen immunotherapy--the only current therapy potentially capable of modifying the underlying allergic disease.

Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy.

BACKGROUND: Biomarkers predicting the safety and efficacy of sublingual immunotherapy (SLIT) remain to be established. METHODS: Eighty-nine patients with allergic rhinoconjunctivitis to grass pollen received either a placebo or five-grass-pollen daily tablet sublingually for 4 months. Following exposure in an allergen challenge chamber, clinical responders and nonresponders were identified individually by evaluating their rhinoconjunctivitis total symptom score (RTSS). Activation of peripheral blood basophils was measured by cytofluorometry before and after 2 or 4 months of immunotherapy, based on CD203c surface expression following allergen stimulation. RESULTS: Patients receiving the grass-pollen tablet had a relative mean improvement of 29.3% vs placebo in the average RTSS after 4 months of SLIT (P < 0.0003). No significant changes in basophil activation were noticed after 2 or 4 months of SLIT despite induction of specific IgGs. Among individual clinical responders, basophil activation was either decreased, increased, or unmodified during SLIT. Levels of basophil activation prior to immunotherapy were not predictive of local adverse reactions associated with immunotherapy. A moderate association was found between basophil activation and allergen-specific IgE levels, skin reactivity, or RTSS, suggesting that the former is, to some extent, indicative of disease severity. As such, patients with the highest level of basophil activation before treatment were more likely to benefit clinically from SLIT. CONCLUSIONS: Allergen reactivity of peripheral blood basophils is not a biomarker for adverse events or early onset of clinical responses to SLIT.

[Travelling families: a nurses' consultation]. / La famille en voyage: une consultation infirmière sur mesure.

In support of the general practitioners and paediatricians of both the private and public sectors, a team of three nurses specialised in Travel Health Medicine offers first line consultations to families about to travel. The team updates basic vaccinations and determines the vaccinations specific to each destination, particularly the yellow fever vaccine, following the recommendations of the Swiss Group of Travel Health Medicine and the Federal Office of Public Health. The nurses inform and prescribe the adequate medication against malaria for parents and children. The consultation is also a place for counselling, where parents can ask questions about various subjects related to their travel. Tact, receptiveness, and reassurance are essential assets of the nurses, allowing for an efficient and useful consultation for the travellers.

Relation between feeding behaviour and energy metabolism in pigs fed diets enriched in dietary fibre and wheat aleurone.

Feed intake and its daily pattern are regulated both at a short and a long term by several control pathways, including energy balance regulation. This trial aimed to determine the effect of dietary fibre (DB) (mix of wheat, soy and sugar beet pulp fibres) and aleurone supplementation and their interaction on energy and nitrogen balances in growing pigs with ad libitum access to feed. Forty pigs (BW: 35 kg) were fed diets differing by fibre concentration (NDF concentration: 10% or 14% DM) and aleurone supplementation (0, 2 or 4 g/kg) during 3 weeks. Pigs were housed individually in a respiration chamber during the last week to record feeding behaviour and measure energy and nitrogen balances (n = 36). Glucose oxidation was studied on the 6th day with an injection of [U-13C] glucose and measurement of 13CO2 production. There was no significant interaction between DB inclusion and aleurone supplementation on any variables characterizing feeding behaviour. Pigs had less but longer meals with high level of DB, with an increased interval between two meals without effect on daily feed intake. The meal frequency significantly decreased when aleurone supplementation increased. Total tract apparent digestibility coefficient of DM, organic matter, ash, nitrogen and gross energy decreased when pigs received high DB level. Dietary fibre level increased significantly faecal excreted nitrogen. Aleurone supplementation decreased nitrogen retention. Free access to the feed induced a great individual variability not only in feed intake level (from 784 to 2290 g/day) but also in feeding behaviour (from 5.5 to 21.5 meals per day). This variability can be linked with the importance of underlying feed intake regulation pathways and difference in energy balance and metabolism efficiency. Several profiles of metabolism efficiency can be discriminate, thanks to a clustering based on feeding behaviour and pre-prandial concentrations of metabolites and hormones. In conclusion, DB inclusion decreased meal frequency, increased average meal size, decreased total tract apparent faecal digestibility coefficient of nitrogen and gross energy. Supplementation of aleurone decreased average daily feed intake with a reduction of the meal number per day, without modification of average meal size. Aleurone supplementation decreased nitrogen retention and nutrient deposition. Independently of experimental diets, the high individual variability permitted discriminating different profiles with different metabolic strategies. Efficient pigs with a high energy retention as protein and lipid seem to be able to adapt their metabolism according to energy sources.

[Diagnosis and treatment of cross-bite in children]. / Les anomalies maxillomandibulaires du sens transversal chez l'enfant.

Transverse maxillomandibular discrepancies are a major component of several malocclusions. They must be prematurely detected and treated. The causes are parafunctional, dysfunctional or kinetic. The different clinical forms encountered are alveolar (endoalveolia) or skeletal (endognathia), which may be associated with a kinetic anomaly. Orthopedic and orthodontic forces are used routinely to correct a maxillary transverse deficiency in a young patient to achieve harmonious growth.

[The functional mandibular prognathism]. / Le proglissement mandibulaire.

The functional mandibular prognathism belong to the class III malocclusion according to the terminology of Angle. Its origins are multiple, from the abnormality of eruption of deciduous or definitive incisors to lingual dysfunction (low position of the tongue). In spite of its weak prevalence, it must be prematurely detected and treated (mixed or temporary teeth) to prevent a functional anomaly to become a skeletal anomaly. It is important at this stage to proceed to the unique gesture which allows making the differential diagnosis: it is the De Névrezé procedure; it allows obtaining a more retrusive position of the mandible to minimize the dental relations. In case of true mandibular prognathism, the maneuver does not succeed; there is no modification of the dental reports. An interceptive therapeutic phase allows finding quickly a previous correct guide and to rehabilitate the growth of jaws.

RSK2 is a new Pim2 target with pro-survival functions in FLT3-ITD-positive acute myeloid leukemia.

Acute myeloid leukemia (AML) with the FLT3 internal tandem duplication (FLT3-ITD AML) accounts for 20-30% of AML cases. This subtype usually responds poorly to conventional therapies, and might become resistant to FLT3 tyrosine kinase inhibitors (TKIs) due to molecular bypass mechanisms. New therapeutic strategies focusing on resistance mechanisms are therefore urgently needed. Pim kinases are FLT3-ITD oncogenic targets that have been implicated in FLT3 TKI resistance. However, their precise biological function downstream of FLT3-ITD requires further investigation. We performed high-throughput transcriptomic and proteomic analyses in Pim2-depleted FLT3-ITD AML cells and found that Pim2 predominantly controlled apoptosis through Bax expression and mitochondria disruption. We identified ribosomal protein S6 kinase A3 (RSK2), a 90 kDa serine/threonine kinase involved in the mitogen-activated protein kinase cascade encoded by the RPS6KA3 gene, as a novel Pim2 target. Ectopic expression of an RPS6KA3 allele rescued the viability of Pim2-depleted cells, supporting the involvement of RSK2 in AML cell survival downstream of Pim2. Finally, we showed that RPS6KA3 knockdown reduced the propagation of human AML cells in vivo in mice. Our results point to RSK2 as a novel Pim2 target with translational therapeutic potential in FLT3-ITD AML.

The cyclin-dependent kinase Cdk5 controls multiple aspects of axon patterning in vivo.

Cyclin-dependent kinase 5 (Cdk5) is one of a subfamily of Cdks involved in the control of cell differentiation and morphology rather than cell division. Specifically, Cdk5 and its activating subunit, p35, have been implicated in growth cone motility during axon extension. Both Cdk5 and p35 are expressed in post-mitotic neurons and are localized to growth cones [1] [2] [3] [4]. The Cdk5-p35 complex interacts with the Rac GTPase, a protein required for growth cone motility [5]. Studies using cultured neurons have suggested that Cdk5 activity controls the efficiency of neurite extension [3] [4]. Mutant mice lacking p35 exhibit subtle axon-guidance defects [6], but these mice have severe defects in neuronal migration [6] [7] [8], making it difficult to define precisely the role of the Cdk5-p35 complex in vivo. Here, we examined Cdk5 function in axon patterning in the Drosophila embryo. Although our data support the idea that Cdk5-p35 is involved in axonogenesis, they do not support the view that Cdk5 simply promotes growth cone motility. Instead, we found that disrupting Cdk5 function caused widespread errors in axon patterning.

The p42/p44 MAP kinase pathway prevents apoptosis induced by anchorage and serum removal.

Anchorage removal like growth factor removal induces apoptosis. In the present study we have characterized signaling pathways that can prevent this cell death using a highly growth factor- and anchorage-dependent line of lung fibroblasts (CCL39). After anchorage removal from exponentially growing cells, annexin V-FITC labeling can be detected after 8 h. Apoptosis was confirmed by analysis of sub-G1 DNA content and Western blotting of the caspase substrate poly (ADP-ribose) polymerase. Growth factor withdrawal accelerates and potentiates suspension-induced cell death. Activation of Raf-1 kinase in suspension cultures of CCL39 or Madin-Darby canine kidney cells stably expressing an estrogen-inducible activated-Raf-1 construct (DeltaRaf-1:ER) suppresses apoptosis induced by growth factor and/or anchorage removal. This protective effect appears to be mediated by the Raf, mitogen- or extracellular signal-regulated kinase kinase (MEK), and mitogen-activated protein kinase module because it is sensitive to pharmacological inhibition of MEK-1 and it can be mimicked by expression of constitutively active MEK-1 in CCL39 cells. Finally, apoptosis induced by disruption of the actin cytoskeleton with the Rho-directed toxin B (Clostridium difficile) is prevented by activation of the DeltaRaf-1:ER chimeric construct. These findings highlight the ability of p42/p44 mitogen-activated protein kinase to generate survival signals that counteract cell death induced by loss of matrix contact, cytoskeletal integrity, and extracellular mitogenic factors.

An anchorage-dependent signal distinct from p42/44 MAP kinase activation is required for cell cycle progression.

Most normal cells require both mitogens and integrin-mediated attachment for growth. It is generally accepted that the p42/p44 MAP kinase module, which can be activated by both growth factors and adhesion, plays a critical role in G0 to S phase progression of quiescent cells. Studies on various cultured fibroblasts have shown that removal of anchorage leads to cell cycle arrest in G1 and it has been proposed that adhesion-dependent G1 progression requires the joint regulation of p42/p44 MAP kinase by integrins and growth factors. In quiescent CCL39 lung fibroblasts, MAP kinase activation in response to serum becomes compromised when cells are placed in suspension. Under these conditions, serum-stimulated cells arrest their growth in mid-G1 with reduced cyclin D1 expression and increased p21Cip/Waf1 expression, as compared to their attached counterparts. To determine whether a casual link exists between suboptimal activation of MAP kinase in non-adherent cells and the observed G1 block, we used a variant of CCL39 stably expressing an estrogen-inducible activated-Raf-1 construct (deltaRaf-1:ER). We found that even strong and sustained activation of MAP kinase with estradiol, in addition to serum, is not able to boost cyclin D1 expression levels or stimulate hyperphosphorylation of pRb in suspended CCL39-deltaRaf-1:ER cells. These results indicate that p42/p44 MAP kinase activation is not a limiting factor for G1 to S phase transit in absence of anchorage. Thus, at least one adhesion-mediated signalling event, distinct from MAP kinase activation is required for maximal cyclin D1 induction and hyperphosphorylation of pRb.

The role of GLUT2 in dietary sugar handling.

GLUT2 is a facilitative glucose transporter located in the plasma membrane of the liver, pancreatic, intestinal, kidney cells as well as in the portal and the hypothalamus areas. Due to its low affinity and high capacity, GLUT2 transports dietary sugars, glucose, fructose and galactose in a large range of physiological concentrations, displaying large bidirectional fluxes in and out the cells. This review focuses on the roles of GLUT2. The first identified function of GLUT2 is its capacity to fuel metabolism and to provide metabolites stimulating the transcription of glucose sensitive genes. Recently, two other functions of GLUT2 are uncovered. First, the insertion of GLUT2 into the apical membrane of enterocytes induces the acute regulation of intestinal sugar absorption after a meal. Second, the GLUT2 protein itself initiates a protein signalling pathway triggering a glucose signal from the plasma membrane to the transcription machinery.

Signaling angiogenesis via p42/p44 MAP kinase and hypoxia.

Angiogenesis is associated with a number of pathological situations. In this study, we have focused our attention on the role of p42/p44 MAP (mitogen-activated protein) kinases and hypoxia in the control of angiogenesis. We demonstrate that p42/p44 MAP kinases play a pivotal role in angiogenesis by exerting a determinant action at three levels: i) persistent activation of p42/p44 MAP kinases abrogates apoptosis; ii) p42/p44 MAP kinase activity is critical for controlling proliferation and growth arrest of confluent endothelial cells; and iii) p42/p44 MAP kinases promote VEGF (vascular endothelial growth factor) expression by activating its transcription via recruitment of the AP-2/Sp1 (activator protein-2) complex on the proximal region (-88/-66) of the VEGF promoter and by direct phosphorylation of hypoxia-inducible factor 1 alpha (HIF-1 alpha). HIF-1 alpha plays a crucial role in the control of HIF-1 activity, which mediates hypoxia-induced VEGF expression. We show that oxygen-regulated HIF-1 alpha protein levels are not affected by intracellular localization (nucleus versus cytoplasm). Finally, we propose a model which suggests an autoregulatory feedback mechanism controlling HIF-1 alpha and therefore HIF-1-dependent gene expression.

Stereoselective synthesis of peptidyl trifluoromethyl alcohols and ketones: inhibitory potency against human leucocyte elastase, cathepsin G, porcine pancreatic elastase and HIV-1 protease.

New fluorinated inhibitors have been designed to target two major proteases-human leucocyte elastase and HIV-1 protease. Two series of beta-peptidyl trifluoromethyl alcohols (TFMAs) Z-L-Val-NH-*CH(Y)*CH(OH)-CF3, where *C is the chiral centre, varied in the nature of the substituent Y, a phenylethyl [-(CH2)2-C6H5] or an isopropyl [-CH(CH3)2] group. These TFMAs were first synthesized as two pairs of the syn and anti diastereoisomers. The inhibitory effects of these mixtures were then assessed on three serine proteases chosen on the basis of the aromatic and aliphatic nature of the substituents-human leucocyte elastase (HLE), human cathepsin G (HCG) and porcine pancreatic elastase (PPE). In the presence of detectable inhibition, each epimer at C2 was separated to determine its inhibition constant (Ki) towards HLE, HCG and PPE. The stereoisomerically pure TFMAs were then oxidized into peptidyl trifluoromethyl ketones (TFMKs) for similar inhibition assays. The absolute configuration of the compounds remained unknown. One epimer at C2 of each syn and anti TFMA with the phenylethyl substituent behaved as a competitive inhibitor towards HLE and HCG with inhibition constants below the millimolar range, whereas their TFMK counterparts were non-inhibitors. In the second series, the two ketones inhibited both elastases with Ki values in the micromolar range, whereas only the syn TFMA was active towards HLE (Ki = 5.65 x 10(-4)M). The tested compounds also had structural properties compatible with recognition by HIV-1 protease. The inhibition of the enzyme was observed with TFMK only (IC50 = 15-200 microM). The phenylethyl substituent promoted inhibition by a factor of 10 (IC50 = 15 microM) compared with the isopropyl substituent (IC50 = 200 microM) leading to selective inhibition of HIV-1 protease. Isomerically pure TFMKs were more potent towards HLE than the alcohols from which they were obtained. However, an enantiomerically pure TFMA selectively inhibited HLE unlike its TFMK analogue which also inhibited PPE. This last result together with the selective inhibition of HIV-1 protease by TFMK with a phenylethyl substituent might be relevant to the design of specific HLE and HIV-1 inhibitors as therapeutic agents.

Effect of ELF pulsed magnetic fields on survival of leukaemia-prone AKR mice.

In a previous experiment an increase in the survival time of leukaemia-prone AKR mice was observed by exposure to a 600 mT or 800 mT static magnetic field when the mice were at least 200 days old. In this experiment 200-day-old-mice were exposed to a 6 mT pulsed magnetic field (PMF) for 30 minutes a day, twice a week until death. The frequency of the field was 12 Hz or 460 Hz. The exposed mice died from leukaemia but had an increased survival time; the average increase was 14.25% compared to the controls. Both the frequencies gave similar results.

[Sustained ventricular tachycardia in older children. Spontaneous regression in 3 cases]. / Tachycardie ventriculaire en salve soutenue du grand enfant. Guérison spontanée de 3 cas.

Extensively described since Gallvardin's reports, the electrical features of salves of ventricular tachycardia in an apparently healthy heart are now well known. The usual benign nature of this arrhythmia is acknowledged, seldom contradicted by isolated clinical cases. Although chronicity is the rule in young adults, there have been a few publications concerning the natural history of these tachycardias in the paediatric age group. The authors report three cases of episodic sustained ventricular tachycardia in older children, presenting at an average of 7 years of age (range 5 to 9 years) and followed up for an average of 7 years (range: 5.5 to 9 years). These three children were treated for an average of 4.5 years (range: 3 to 5.5 years). All treatment was finally withdrawn when stable permanent sinus rhythm without ventricular extrasystoles was restored and confirmed over an average period of 2 years (range 10 months to 3.5 years), an average of 4 (range 3 to 7) successive normal Holter recordings at several months' interval. The outcome in children to spontaneous regression after several years would seem to make radiofrequency ablation more dangerous than useful given the benign nature of the arrhythmia and its good response to pharmacological intervention.

[Vagal hyperreactivity and sudden infant death. Study of 15 families]. / Hyperréactivité vagale et mort subite dans la fratrie. Etude des 15 familles.

Prone sleep position is obviously the main risk factor for sudden infant death. Other risk factors, such as vagal overactivity particularly in the familial form, are still discussed. We here report 15 families characterized by the coexistence of vagal overactivity and sudden infant death. At least, 1 child for each family had documented [Holter or occulo-cardiac reflex (OCR)] vagal overactivity. In 5 families 2 children were affected; in 2 families 3 children were affected and in 1 family 4 children were affected. Sudden death occurred in the elderly of the family in 8 cases, in the twin in 3 cases, in the 2nd in 3 cases and in the 5th child in 1 case. Within the 15 families, at least 1 parent had experienced vagally-induced fainting or syncope in 10 cases. Familial pattern of vagal overactivity is underlined. Possible links between vagal overactivity, risk factor for suddden death and sudden death are discussed. We suggest an Holter-ECG and OCR follow-up for sudden infant death siblings with history of familial vagal overactivity (3 examinations during the 1st year of life, at 1, 3 and 9 months).