L’indication d’une cystographie après une première infection urinaire fébrile (IUF) n’est plus systématique, cependant le dépistage des reflux vésico-urétéraux (RVU) de haut grade (≥III) reste ...important pour l’avenir rénal des malades. Après avoir instauré un protocole local limitant les indications de cystographies après une IUF, nous avons voulu vérifier qu’il n’induisait pas de sous-diagnostic des RVU de haut grade.
Étude rétrospective comparant le nombre de RVU diagnostiqués sur 2 périodes de 1 an, chez des enfants âgés de 1 mois à 18ans ayant été pris en charge par le service des urgences pédiatriques du centre hospitalier universitaire (CHU) de Reims pour une première IUF. La première (période 0) où tous les malades avaient une cystographie et la seconde (période 1) où elle n’était réalisée que chez les enfants ayant une procalcitonine supérieure à 1ng/L ou une anomalie rénale échographique.
Durant la période 0, les 100 enfants inclus ont eu une cystographie et 7 RVU de haut grade ont été diagnostiqués. Durant la période 1, 102 enfants ont été inclus, 52 cystographies ont été réalisées et 8 RVU de haut grade ont été diagnostiqués. Les RVU de bas grade (I et II) ont été moins souvent dépistés, sans conséquences pour les enfants.
Ce protocole a permis, sans sous-diagnostiquer les RVU de haut grade, une diminution de 40 % des prescriptions de cystographie. Le nombre de cystographies normales est malgré tout resté élevé.
Whether or not voiding cystourethrography (VCUG) should be performed after a first episode of urinary tract infection (UTI) remains a matter of debate. The role of VCUG is primarily to diagnose high-grade vesicoureteral reflux (≥grade III) (VUR) and hence prevent the development of renal scars and poor long-term outcome. We designed a protocol designed to reduce the indications for performing unnecessary VCUGs after a first episode of febrile UTI. In order to evaluate the efficacy of our protocol, we designed a retrospective study to verify whether high-grade VUR was subsequently being underdiagnosed.
This study compared the number of cases of VUR diagnosed over 2 1-year periods in children aged 1month to 18years. Data were collected from records held in the pediatric emergency department of the University Hospital of Reims. All cases included had presented to the department with a first episode of febrile UTI. During the first 1-year collection period, all patients underwent a VCUG. During the second collection period, the protocol was in place and VCUG was only performed in children with a serum procalcitonin level greater than 1ng/L and/or an abnormal renal ultrasound scan.
During the first year, 100 patients underwent routine VCUG and 7 cases of high-grade VUR were diagnosed. During the following year, VCUG was limited according to the new protocol: 102 patients were enrolled, 52 VCUGs were performed and 8 cases of high-grade VUR were diagnosed. Cases of low-grade VUR (I and II) were less frequently detected, without significant consequences for the patients.
The protocol led to a 40% decrease in the number of VCUGs performed. No cases of high-grade VUR were missed; however, the number of VCUGs performed with a normal outcome remained significant.
Les mucopolysaccharidoses (MPS) sont dues au déficit d’enzymes intervenant dans le catabolisme des glycosaminoglycanes (GAG) et elles sont caractérisées par des atteintes viscérales multiples ...impliquant souvent le système nerveux central. Malgré leur statut de maladie rare, elles bénéficient d’ores et déjà d’approches thérapeutiques. L’une d’elles est la thérapie substitutive qui consiste à apporter l’enzyme manquante sous la forme d’une molécule recombinante administrée par voie intraveineuse. L’efficacité de cette thérapie repose sur le recaptage des enzymes par les différents tissus par le biais des récepteurs mannose-6-phosphate. Elle est disponible actuellement pour les MPS I, II, VI et d’autres maladies pourraient y avoir accès dans le futur. Pour la MPS I, une autre alternative est la transplantation de cellules souches hématopoïétiques dont les indications doivent être parfaitement définies, notamment compte tenu des risques inhérents à la procédure. D’autres stratégies thérapeutiques innovantes sont actuellement explorées, telle que la thérapie par réduction de substrats basée sur l’utilisation d’inhibiteurs de la biosynthèse des GAG, (génistéine,…) qui permettraient de réduire l’accumulation des composés pathologiques et leurs conséquences au niveau des tissus. D’autres thérapies moléculaires pouvant avoir un effet chaperon ou permettant la translecture de codon stop sont également à l’étude. Enfin, la thérapie génique basée sur l’apport d’un gène normal par l’intermédiaire d’un vecteur viral soit directement, soit à l’aide de cellules génétiquement modifiées, pourrait être une méthode envisageable dans le futur (premiers essais cliniques en cours).
Mucopolysaccharidoses (MPS) are caused by a deficiency of enzymes involved in the catabolism of glycosaminoglycans (GAGs) and are multisystemic diseases, often including the central nervous system. Despite their rare prevalence, specific treatments for MPS are available. One of them is enzyme replacement therapy, which provides the missing enzyme in the form of a recombinant protein administered intravenously. The effectiveness of this treatment relies on the enzymes being taken up by the different tissues via mannose-6-phosphate receptors. Treatment is currently available for MPS I, II and VI, and may be available for other forms of the disease in the near future. An alternative in MPS I is hematopoietic stem cell transplantation, the indications for which must be very clearly defined, particularly given the inherent risks of the procedure. Other new treatment strategies are currently being investigated, including substrate reduction therapy which uses GAG biosynthesis inhibitors (genistein,...), which reduces the accumulation of pathological compounds and their repercussions on tissues. Other molecular therapies using molecular chaperones or read-through molecules for stop codon mutations are also being studied. Finally, gene therapy, by introducing a normal gene sequence through a viral vector, either directly or using genetically modified cells, is a potential future method (the first clinical trials are undergoing).
The convection-permitting regional climate model CNRM-AROME was applied on a spatial domain restricted to the northern half of France for analyzing its performances in simulating the urban climate of ...Paris region, and its potential added value compared to the regional climate model CNRM-ALADIN. In addition to its fine horizontal resolution (2.5 km compared to 12.5 km for CNRM-ALADIN), CNRM-AROME has the advantage of integrating the urban canopy model TEB into its land-surface modeling system. A hindcast simulation was performed for the past period 2000–2017, following an evaluation configuration for which CNRM-AROME was driven by CNRM-ALADIN, driven itself by the ERA-Interim reanalyses. Long-term gridded observations with kilometric resolution allowed a fine spatial scale evaluation of the atmospheric variables simulated by both models. They showed in particular a significant overestimation of spring precipitation, but an improvement of summer precipitation in CNRM-AROME compared to CNRM-ALADIN. Above all, thanks to its horizontal resolution and the use of a dedicated urban model, CNRM-AROME was shown to offer significant added value for the simulation of urban heat islands, for the mapping of heat-warming areas, and for representing the effects of the city on precipitation. It is a promising tool to diagnose climatic and impact indicators at the city scale, and their evolution in a changing climate.
Mucopolysaccharidoses (MPS) are caused by a deficiency of enzymes involved in the catabolism of glycosaminoglycans (GAGs) and are multisystemic diseases, often including the central nervous system. ...Despite their rare prevalence, specific treatments for MPS are available. One of them is enzyme replacement therapy, which provides the missing enzyme in the form of a recombinant protein administered intravenously. The effectiveness of this treatment relies on the enzymes being taken up by the different tissues via mannose-6-phosphate receptors. Treatment is currently available for MPS I, II and VI, and may be available for other forms of the disease in the near future. An alternative in MPS I is hematopoietic stem cell transplantation, the indications for which must be very clearly defined, particularly given the inherent risks of the procedure. Other new treatment strategies are currently being investigated, including substrate reduction therapy which uses GAG biosynthesis inhibitors (genistein,...), which reduces the accumulation of pathological compounds and their repercussions on tissues. Other molecular therapies using molecular chaperones or read-through molecules for stop codon mutations are also being studied. Finally, gene therapy, by introducing a normal gene sequence through a viral vector, either directly or using genetically modified cells, is a potential future method (the first clinical trials are undergoing).
Not only is ecological specialization a defining feature of much of Earth's biological diversity, the evolution of specialization may also play a central role in generating diversity by facilitating ...speciation. To understand how ecological specialization evolves, we must know the particular characters that cause organisms to be specialized. For example, most theories of specialization in herbivorous insects emphasize physiological trade‐offs in response to toxic plant chemicals. However, even in herbivores, it is likely that other characters are also involved in resource specialization. Knowing the causes of ecological specialization is also crucial for linking specialization to speciation. When the same character(s) that cause specialization also influence assortative mating, speciation may occur particularly rapidly because specialization and reproductive isolation become coupled in a positive feedback that speeds the evolution of both. Indeed, a central hypothesis in the study of ecological speciation is that specialization in recently diverged taxa may often be due to characters that also produce assortative mating. We test this hypothesis by evaluating the causes of ecological specialization among host‐associated populations of an herbivorous insect, the pea aphid (Acyrthosiphon pisum). These populations are highly specialized on different host plants (alfalfa or clover; “alternate hosts”), and the races are partially reproductively isolated. Here, we identify key characters responsible for host plant specialization. Our results suggest that the major proximal determinant of host specialization is the behavioral acceptance of a plant rather than the toxicity of the food source. Pea aphids rapidly assess alfalfa and clover and reject the alternate host based on chemical cues that are perceived before the initiation of feeding. This rapid behavioral rejection of the alternate host by a given race has two consequences. First, unrestrained aphids quickly leave the alternate host and search for other plants. Because pea aphids mate on their host plants, divergence in host acceptance among ecologically specialized races leads to congregation on the favored host. This results in de facto assortative mating when sexual forms are produced in late summer. Second, specialized aphids that are held on the alternate host will not feed in a 7.2‐h trial, even in the face of starvation. Thus, a complex trait, behavioral acceptance of a plant as host, influences both reproductive isolation (through host‐associated assortative mating) and ecological specialization (because of low nutritional uptake on the alternate host). This dual influence of feeding behavior on both assortative mating and resource specialization is central to the maintenance of these divergent races, and it may also have been involved in their origin.
Pompe disease is a lysosomal storage disorder caused by acid-α-glucosidase (GAA) deficiency, leading to glycogen storage. The disease manifests as a fatal cardiomyopathy in infantile form. Enzyme ...replacement therapy (ERT) has recently prolonged the lifespan of these patients, revealing a new natural history. The neurologic phenotype and the persistence of selective muscular weakness in some patients could be attributed to the central nervous system (CNS) storage uncorrected by ERT. GAA-KO 6neo/6neo mice were treated with a single intrathecal administration of adeno-associated recombinant vector (AAV) mediated gene transfer of human GAA at 1 month and their neurologic, neuromuscular, and cardiac function was assessed for 1 year. We demonstrate a significant functional neurologic correction in treated animals from 4 months onward, a neuromuscular improvement from 9 months onward, and a correction of the hypertrophic cardiomyopathy at 12 months. The regions most affected by the disease i.e. the brainstem, spinal cord, and the left cardiac ventricular wall all show enzymatic, biochemical and histological correction. Muscle glycogen storage is not affected by the treatment, thus suggesting that the restoration of muscle functionality is directly related to the CNS correction. This unprecedented global and long-term CNS and cardiac cure offer new perspectives for the management of patients.
Le traitement par enzymothérapie des maladies lysosomales Valayannopoulos, V.; Brassier, A.; Chabli, A. ...
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
10/2011, Letnik:
18, Številka:
10
Journal Article
Recenzirano
Récemment, des progrès considérables ont été réalisés dans le domaine des maladies lysosomales. Dans le passé aucun traitement spécifique n’était disponible pour les patients ; la prise en charge ...consistait en un traitement symptomatique et au traitement des complications. Progressivement des traitements spécifiques de substitution enzymatique qualifiés de « médicaments orphelins » ont fait leur apparition pour certaines de ces maladies et plus particulièrement pour la maladie de Gaucher, la maladie de Fabry, les mucopolysaccharidoses de type I, II et VI et pour la maladie de Pompe. Dans cette revue nous allons résumer les bénéfices cliniques et les inconvénients de chacune de ces thérapeutiques et nous allons également décrire de nouvelles perspectives thérapeutiques en cours de développement dans le domaine de l’enzymothérapie substitutive.
In the last years, much progress has been achieved in the treatment of lysosomal storage disorders. Until recently only symptomatic treatment was available for the affected patients. Progressively enzyme replacement treatments have been developed for several diseases, namely Gaucher disease, Fabry disease, mucopolysaccharidoses type I, II and VI and Pompe disease. In this review we will summarize the efficacy and safety of these treatments and describe new therapeutic trials for other lysosomal storage disorders or perspectives in the use of currently available treatments.
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