Case Report:Inactivating PTH/PTHrP Signaling Disorder Type 1 Presenting With PTH Resistance

peer reviewedPTH resistance is characterized by elevated parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia and it is classically associated with GNAS locus genetic or epigenetic defects. Inactivating PTH/PTHrP signaling disorders (iPPSD) define overlapping phenotypes based on their molecular etiology. iPPSD1 is associated with PTH1R variants and variable phenotypes including ossification anomalies and primary failure of tooth eruption but no endocrine disorder. Here we report on a 10-month-old child born from consanguineous parents, who presented with mild neurodevelopmental delay, seizures, enlarged fontanelles, round face, and bilateral clinodactyly. Hand x-rays showed diffuse delayed bone age, osteopenia, short metacarpal bones and cone-shaped distal phalanges. A diagnosis of PTH resistance was made on the basis of severe hypocalcemia, hyperphosphatemia, elevated PTH and normal vitamin D levels on blood sample. The patient was treated with calcium carbonate and alfacalcidol leading to rapid bio-clinical improvement. Follow-up revealed multiple agenesis of primary teeth and delayed teeth eruption, as well as Arnold-Chiari type 1 malformation requiring a ventriculoperitoneal shunt placement. GNAS gene analysis showed no pathogenic variation, but a likely pathogenic homozygous substitution c.723C>G p.(Asp241Glu) in PTH1R gene was found by trio-based whole exome sequencing. We studied the deleterious impact of the variant on the protein conformation with bioinformatics tools. In conclusion, our study reports for the first time PTH resistance in a child with a biallelic PTH1R mutation, extending thereby the clinical spectrum of iPPSD1 phenotypes

Plasma level monitoring of the major metabolites of diacetylmorphine (heroin) by the "chasing the dragon" route in severe heroin addicts

peer reviewedThe objective of the present study was to verify if severe physical health problems frequently encountered in heroin addicts and the concomitant use of alcohol and legal or illegal drugs other than heroin influenced the pharmacokinetics of the major metabolites of heroin. We conducted a 90 minutes follow-up of the plasma concentrations of the pharmaceutical heroin, named diacetylmorphine (DAM), in patients recruited in a DAM assisted treatment centre. TADAM (Traitement Assisté par DiAcétylMorphine) aimed to compare the efficacy of heroin-assisted treatment (HAT) compared with methadone maintenance treatment (MMT) for heroin users considered as treatment resistant patients and who have severe physical and mental health problems. Eleven patients were recruited. Blood samples were collected at baseline and 15, 45 and 90 minutes after DAM administration. All patients received DAM by the "chasing the dragon" route. Plasma samples were analyzed by a previously described ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS) method. A principal component analysis (PCA) was performed and 8 metabolite concentrations ratios were calculated to evaluate the influence of various factors (DAM dose, patient pathologies, concomitant use of medications, methadone, street heroin, alcohol and cocaine) on heroin metabolite pharmacokinetics. It seemed to be not affected by the DAM dose, patient pathologies and the concomitant use of medications, methadone, street heroin and alcohol. Cocaine use was the only parameter which showed differences in heroin pharmacokinetics

L'alcool rapporte-t-il à la société plus qu'il ne lui coûte ?

peer reviewedL’alcool remonte le moral. Une petite cuite n’a jamais tué personne. Boire un café atténue l’effet de l’alcool. Le binge drinking est un fléau nouveau… De nombreuses idées reçues, certaines fondées, d’autres pas, sont véhiculées à propos de l’alcool et de ses conséquences. L’alcool soulève aussi de multiples questions : L’alcool est-il une drogue ? L’alcool est-il aphrodisiaque ? L’alcoolisme est-il héréditaire ? Combien l’alcool coûte/rapporte-t-il à la société ? Peut-on guérir de l’alcoolisme ?… Ce livre a pour but de démont(r)er certaines idées reçues sur l’alcool et d’apporter des réponses aux questions que chacun se pose. Les auteurs ne se bornent pas à répondre par vrai ou faux, ils fournissent les explications, appuyées sur l’état des connaissances scientifiques actuelles, qui permettent d’infirmer ou de confirmer ces idées reçues ou de répondre à ces questions. Ils nuancent le propos lorsque la réponse n’est pas de l’ordre du tout ou rien. Il est indéniable que l’excès d’alcool est nuisible à la santé. Il existe cependant une littérature scientifique démontrant des effets positifs sur la santé de la consommation en quantités modérées de certaines boissons alcoolisées. Ce mélange d’effets positifs et négatifs explique que le public a développé une relation d’amour-haine avec l’alcool. Ainsi, les abstinents complets sont parfois qualifiés de rabat-joie. Les alcooliques chroniques (5 à 10 % des occidentaux, selon les études épidémiologiques !) sont, quant à eux, souvent trop vite jugés. Ce qui est certain c’est que l’alcoolo-dépendance est source de beaucoup de souffrances pour la personne et son entourage. Ces 41 réponses à des questions sur l’alcool visent à donner des balises au lecteur, littérature scientifique à l’appui

Projet TADAM: Conclusions scientifiques et recommandations

Projet TADAM, un projet pilote de traitement assisté par diacétylmorphin

Hypersensibilité électromagnétique et exposition professionnelle aux champs électromagnétiques

Introduction Scientific publications on electromagnetic hypersensitivity began in the early 80' and were first related to video display terminals in the professional environment. Electromagnetic hypersensitivity is now more heterogeneous and complaints about electromagnetic fields (EMF) are often associated to mobile phone or wifi. Provocation studies did not find that persons claiming to have electromagnetic hypersensitivity were more able to detect EMF than others or that they displayed any special physiological changes when exposed to EMF. Since 1996, WHO defined this syndrome as Idiopathic Environmental Intolerance to ElectroMagnetic Fields (IEI-EMF), characterised by symptoms attributed to EMF. The diagnostic is made by the person itself. The symptoms are heterogeneous and are frequently encountered in the general population. Despite the lack of a proven causal relationship with EMF, these symptoms, and the anxiety related, can lead to important suffering. Some persons with IEI-EMF are even unable to work. IEI-EMF is classified among the functional somatic syndromes as other syndromes with no physiological basis (as multiple chemical sensitivity). Directive and IEI-EMF Studies showed that persons who feel more stressed in their professional environment and are less satisfied with their work are more prone to IEI-EMF. There are some elements in the directive that could frighten these persons: the directive does not consider long term effects; the limit values can be exceeded temporarily and a worker must be informed that he can have transient symptoms. Discussion Persons with IEI-EMF are afraid of adverse health effects and often think that these effects are not taken into account by official agency. For them, everything that can aggravate their fears will be difficult to handle.Etude EPI - Etude Psychoneuroendocrinienne de l'Intolérance Environnementale Idiopathique aux champs électromagnétique

Feasibility and efficacy of diacetymorphine-assisted treatment in Belgium

Objective The aim of our research was to assess the feasibility and efficacy of a treatment assisted by diacetylmorphine in Liège. This treatment is offered to persons dependent on heroin who pursue street heroin use despite existing treatments. Methods Data were collected in a pilot project of Treatment Assisted by Diacetylmorphine (TADAM), which took place in Liège from 2007 to 2013. The heart of this project is a randomised controlled trial comparing a diacetylmorphine treatment – limited to 12 months – with existing methadone treatments. A participant was responder if he/she showed improvement on the level of street heroin use, health or criminal involvement. Other researches (mainly based on interviews) were added in order to understand interactions between the trial and its actors: heroin users (included or not-included), neighbours of the DAM centre, the staff of the DAM centre and staff of other institutions who worked with our target group in Liège. Results With the help of the centres, partners of the trial, 74 participants (of the 200 planned) were included and randomised: 36 in the experimental group and 38 in the control group. These participants were dependent on heroin for 20 years on average and had already tried 9 treatments for their addiction(s). At the end of the trial, the number of responders in the experimental group was greater but not significantly than in the control group (p=0.35). However, participants in the experimental group showed greater improvement than in the control group, on the level of street heroin use (p=0.0011) and physical (p=0.043) or mental (p=0.035) health. During the follow-up study, three months after the end of the 12 months of treatment, street heroin use in the experimental group had significantly increased (p=0.0052) and the difference with the control group was no longer significant (p=0.55). Discussion Participants included in the trial were, as expected, persons severely dependent on street heroin, who could not find a solution to their addiction with the existing treatments. Participants in the experimental group decreased significantly their street heroin use. However, in our follow-up study, street heroin use increased significantly in the experimental group 3 months after the end of the diacetylmorphine treatment. In the foreign studies, diacetylmorphine treatment showed greater efficacy compared to methadone treatment for this target group and the improvement was sustained after the trial even when the treatment was stopped, but not when the end of treatment was forced against the will of the patient. Nevertheless, our research showed the feasibility of a diacetylmorphine treatment in Liège and its acceptance by the actors involved in the trial. Conclusion Diacetylmorphine treatment is feasible in Belgium. In foreign studies, it showed more efficacy than methadone treatment and benefits gained with this approach were maintained during years. But these benefits disappear when the end of treatment is forced, against the will of the patient

Idiopathic Environmental Intolerance attributed to electromagnetic fields (IEI-EMF)

Depuis le début des années '80, des chercheurs étudient les plaintes des personnes se disant hypersensibles aux champs électromagnétiques (EMF), sous les normes recommandées. Les recherches n'ont cependant pas démontré que ces personnes étaient capables de détecter les EMF ni qu'elles présentaient des changements physiologiques en étant exposées aux EMF . L'OMS a regroupé ces plaintes sous le nom d'Intolérance Environnementale Idiopathique attribuée aux Champs Electromagnétiques (IEI-EMF). Au niveau médical, l'IEI-EMF est classée parmi les syndromes fonctionnels somatiques comme d'autres syndromes sans bases physiologiques démontrées.Etude de l'intolérance environnementale idiopathique attribuée aux champs électromagnétique

TADAM Traitement Assisté par DiAcétylMorphine: Profil des patients

Background : TADAM est une étude contrôlée randomisée comparant un traitement par héroïne (HAT) avec des traitements par méthadone existants. Ce projet est toujours en cours mais nous disposons déjà de données sur les patients au moment de leur inclusion. Nous analysons leur profil, particulièrement leurs caractéristiques criminologiques, et nous le comparons avec celui des participants aux autres expériences HAT. Méthodologie : Lors de l’inclusion, chaque patient a répondu à des questionnaires standardisés ainsi qu’à un questionnaire de délinquance et de victimisation auto-rapportées. Comme point de comparaison, nous avons sélectionné trois études européennes contrôlées randomisées sur le HAT. Nous avons ajouté une étude suisse, sans groupe contrôle, évaluant les effets de la prescription d’héroïne sur la délinquance des patients. Résultats : Nos patients sont plus âgés et plus souvent de sexe masculin. Ils bénéficient plus souvent d’allocations sociales et ont connu plus de traitements pour un problème d'addiction. Ces patients avaient un passé judiciaire aussi important qu’à l’étranger. Sur les six derniers mois, ils sont moins nombreux à avoir commis des actes délinquants mais le nombre d'actes commis est plus important. Les faits sont surtout liés à la drogue ou à la propriété. Conclusion : Nos patients étaient moins nombreux à être délinquants mais il y aurait plus de professionnalisation qu'à l'étranger. Le plus petit nombre de délinquants pourrait s'expliquer par la moyenne d'âge plus élevée de nos patients, la plus grande proportion d'allocataires sociaux ou encore par le recours plus important à des traitements pour leur(s) addiction(s).TADAM, un projet pilote de traitement par diacétylmorphin

Prerequisites for the implementation of a new heroin-assisted centre

Prerequisites for the implementation of a new heroin-assisted centre Background: TADAM, a randomised controlled trial of heroin-assisted treatment, will begin in Liège, Belgium, in 2010. Heroin-assisted treatment of treatment resistant heroin addicts has been successfully tested in six countries: Switzerland, The Netherlands, Spain, Germany, Canada and United-Kingdom. Each country used a randomised controlled trial to assess this new treatment. It has now a strong evidence-based foundation. However in the peer-reviewed articles, there is little information on the concrete conditions to fulfil before implementing this treatment. With the experience of the other countries and ours, we have listed those conditions. Methodology: We collected information concerning the randomised controlled trial. This included articles published in international peer-review journals, reports, visits to heroin-assisted treatment centres and information given by researchers who participated in those experiments. We will illustrate our presentation with the example of Liège. Results: Before all, a political agreement at the national level is mandatory. It is never guaranteed even if it was already given in the past. Methadone treatments must be available and the collaboration with the addiction network will be an advantage for the project. There must be a sufficiently high number of heroin addicted in the concerned area and they must be correctly informed about the heroin-assisted treatment. But even if it is the case, the inclusion of the foreseen number of patients can be more difficult than expected because it is problematic to assess the exact number of patients fulfilling the inclusion criteria and because not all the eligible participants will accept to enter this treatment. Conclusion: For reasons other than medical or scientific ones, implementing a new heroin-assisted centre is still a challenge.TADA