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Base de données mondiale pour les patients atteints de blessures ou de maladies rares et importantes ?

Base de données mondiale pour les patients atteints de blessures ou de maladies rares et importantes ?


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Je lisais récemment The Quest for Consciousness de Christof Koch, et il a mentionné à plusieurs reprises à quel point certains patients souffrant de lésions cérébrales tristes et terribles étaient importants pour la compréhension du fonctionnement du cerveau.

Cela m'a fait me demander comment des chercheurs sur le cerveau comme Koch et d'autres trouvent de tels patients. Je m'attends à ce que seul un petit nombre rencontre un chercheur expert en cerveau qui comprend que ce patient pourrait être important pour la recherche sur le cerveau, en particulier pour ces personnes dans les pays moins développés.

Plus généralement, je me pose la même question pour les patients atteints de blessures ou de maladies très rares, qui pourraient potentiellement être importantes pour la recherche en médecine et en biologie :

Existe-t-il une base de données mondiale pour les patients atteints de maladies ou de blessures très rares, permettant aux experts médicaux dans le domaine de les trouver ?

Même si l'expert ne peut pas aider la personne individuelle, j'imagine que de tels patients pourraient être très importants pour la future compréhension/guérison de la blessure/maladie. J'espère obtenir des références bibliographiques ou des suggestions.


Le projet d'échange MatchMaker est une approche fédérée qui permet aux cliniciens de trouver des cas correspondants en fonction de la similitude génétique ou phénotypique, tout en préservant la confidentialité du patient.


Le réseau des maladies non diagnostiquées est similaire à ce que vous recherchez ; ce n'est pas pour les blessures, mais plutôt pour les maladies génétiques rares.


Je ne sais pas s'il existe une base de données mondiale comme celle à laquelle vous pensez, mais Crowdmed.com est un site Web sur lequel les patients publient leurs propres cas médicaux obscurs et publient une prime pour que les chercheurs tentent de les résoudre.


Liste des registres

Un registre est une collection d'informations sur des personnes, généralement axées sur un diagnostic ou une condition spécifique. De nombreux registres recueillent des informations sur les personnes atteintes d'une maladie ou d'un état spécifique, tandis que d'autres recherchent des participants d'états de santé variés qui peuvent être disposés à participer à la recherche sur une maladie particulière. Les individus fournissent des informations sur eux-mêmes à ces registres sur une base volontaire. Les registres peuvent être parrainés par une agence gouvernementale, une organisation à but non lucratif, un établissement de santé ou une entreprise privée. Il est toujours bon de vérifier d'abord qui parraine le registre - ou - de rechercher des informations sur le site d'un registre pour connaître leur(s) parrain(s).

Pourquoi les registres sont-ils nécessaires ?

Les registres peuvent fournir aux professionnels de la santé et aux chercheurs des informations de première main sur les personnes atteintes de certaines conditions, à la fois individuellement et en groupe, et au fil du temps, afin d'améliorer notre compréhension de cette condition. Certains registres collectent des informations qui peuvent être utilisées pour suivre les tendances concernant le nombre de personnes atteintes de maladies, de traitements, etc. D'autres registres invitent les gens à s'inscrire pour être contactés au sujet de la participation à la recherche clinique. Ceux-ci posent des questions très basiques sur les antécédents médicaux qui aideraient à déterminer si une personne est éventuellement éligible pour participer à une étude de recherche.

Il semble que ces registres recueillent des renseignements personnels sur la santé. Existe-t-il un risque que de telles informations soient divulguées ?

Les agences gouvernementales ont des exigences strictes en matière de confidentialité fixées par la loi, telles que la loi fédérale sur la gestion de la sécurité de l'information (FISMA) et la loi sur la portabilité et la responsabilité en matière d'assurance-maladie (HIPAA). Si les registres ont suivi toutes ces règles, la probabilité que des informations personnelles identifiables soient partagées est très faible.

Quels avantages une personne recevra-t-elle en participant à un registre ?

La participation à un registre est susceptible d'augmenter ce que nous savons sur une condition spécifique, d'aider les professionnels de la santé à améliorer le traitement et de permettre aux chercheurs de concevoir de meilleures études sur une condition particulière, y compris le développement et l'essai de nouveaux traitements. Faire partie d'un registre d'essais cliniques peut aider les personnes intéressées à participer à la recherche à entrer en contact avec des chercheurs cliniques. Cependant, les individus (et leurs familles) qui choisissent de participer à un registre doivent comprendre que la participation ne garantira pas un traitement ou une guérison pour leur état ou qu'ils seront éligibles pour participer à une étude.

Qui a accès aux informations d'un registre ?

Habituellement, un registre financé par le gouvernement fédéral a une liste très limitée de personnes (coordinateur du registre) qui peuvent avoir accès aux informations personnelles et d'identification des participants. Ces personnes doivent être spécialement formées et certifiées en ce qui concerne les exigences en matière de sécurité de l'information.

A qui appartiennent les données d'un registre ? Qui prend les décisions sur la façon dont ces données seront utilisées ?

Les données recueillies dans un registre des maladies sont dépouillées des informations personnelles. Il appartient au commanditaire du registre et, selon la façon dont le registre est mis en place, peut être partagé avec les participants et leurs familles, ainsi qu'avec des professionnels de la santé et des chercheurs agréés. Cependant, les informations personnelles et d'identification restent confidentielles. Habituellement, un registre a un comité directeur qui prend des décisions sur la façon dont les données peuvent être utilisées ou partagées.

Un participant peut-il se retirer du registre ?

Oui. Les registres sont gratuits et volontaires, il n'y a aucune pénalité pour choisir de se retirer à tout moment.

À qui le participant doit-il s'adresser pour toute question ou préoccupation supplémentaire ?

Pour toute question concernant la participation ou tout problème pouvant survenir, les registres fournissent un contact, généralement le coordinateur du registre.

En quoi un registre est-il différent d'un essai clinique ?

Les registres axés sur des maladies ou des affections spécifiques collectent volontairement des informations auprès des personnes atteintes de ces affections. Les registres d'essais cliniques recueillent des informations de santé de base auprès des personnes qui acceptent d'être contactées pour participer à de futurs essais ou études cliniques.

Un essai clinique est l'étude de nouvelles façons de prévenir, de détecter ou de traiter des maladies ou des affections. Être volontaire pour un registre ne signifie pas qu'une personne s'est inscrite pour un essai clinique. La participation à un registre de maladies peut parfois devenir une première étape vers la participation à un essai clinique, mais les registres et les essais spécifiques ne sont pas directement liés.

Clause de non-responsabilité: La liste suivante n'est pas destinée à être exhaustive, et l'inclusion d'une organisation particulière sur cette liste n'implique pas l'approbation par les National Institutes of Health ou le ministère de la Santé et des Services sociaux. Notre intention est de fournir des informations sur les efforts de registre au niveau national et n'a donc pas inclus de nombreux groupes locaux qui peuvent offrir une aide précieuse aux individus et à leurs familles dans une zone géographique limitée.



Nous comprenons que chaque progrès scientifique compte lorsqu'il s'agit d'apporter de nouveaux médicaments à ceux qui en ont besoin. Sur les 7 000 maladies rares connues, moins de 5 % ont une option de traitement approuvée. 1 Cette lacune dans les soins a stimulé un sentiment d'urgence : trouver aujourd'hui de nouvelles approches susceptibles de changer la vie.

Pfizer Rare Disease allie une science pionnière à une compréhension approfondie de la pathologie sous-jacente pour proposer des traitements innovants. Avec plus de trois décennies d'expérience dans les maladies rares, notre vaste portefeuille mondial de maladies rares vise à répondre aux besoins médicaux non satisfaits dans un certain nombre de domaines thérapeutiques, notamment l'hématologie, la neurologie, l'endocrinologie, la cardiologie et les maladies métaboliques héréditaires.

Thérapie génique

Quatre maladies rares sur cinq sont génétiques 1 , c'est pourquoi Pfizer explore une nouvelle approche potentiellement transformatrice pour traiter les maladies génétiques grâce à la thérapie génique. Nous sommes bien placés pour mener des avancées dans la recherche en thérapie génique grâce à notre expertise scientifique, notre portée mondiale et plus de trois décennies d'expérience dans les maladies rares.

Notre approche de la thérapie génique fonctionne en délivrant un gène fonctionnel à un tissu ciblé dans le corps, permettant potentiellement au tissu de produire une protéine manquante ou non fonctionnelle chez les patients atteints de certaines maladies génétiques.

Pfizer Rare Disease se concentre sur le développement de thérapies géniques ciblant avec précision le virus adéno-associé recombinant (rAAV), en raison de son potentiel à cibler systématiquement les cellules avec le traitement. Cette technologie peut être standardisée et personnalisée, et a le potentiel de rationaliser le processus de fabrication et de réglementation vers une approbation plus efficace des médicaments.

Actuellement, nous accordons la priorité aux maladies monogéniques, telles que la dystrophie musculaire de Duchenne (DMD), l'hémophilie et la sclérose latérale amyotrophique (SLA), et nous disposons d'un solide portefeuille de traitements potentiels de thérapie génique en développement préclinique et clinique. À l'avenir, nous espérons appliquer notre technologie de thérapie génique au traitement de maladies plus courantes et complexes, où plusieurs gènes sont impliqués, telles que les maladies du système nerveux central et les maladies cardiaques.

Nous sommes ici pour apprendre et stimuler l'innovation grâce à une collaboration et un partenariat actifs :

  • Avec l'acquisition de Bambou Thérapeutique en 2016, nous avons élargi notre portefeuille pour faire progresser la technologie de thérapie génique basée sur l'AAV recombinant et avons notre premier candidat en phase de développement clinique. Notre essai clinique de Phase 1b pour PF-06939926, un candidat de thérapie génique pour la DMD, est en cours, et notre essai clinique de Phase 3 sera initié en 2021.
  • Suite au transfert de la responsabilité du programme de Spark Therapeutics à Pfizer, nous avons lancé notre programme pivot de phase 3, qui évalue la thérapie génique expérimentale fidanacogene elaparvovec pour le traitement de l'hémophilie B.
  • Nous avons également un accord de collaboration et de licence exclusif et mondial avec Sangamo Therapeutics, Inc. pour le développement et la commercialisation de programmes de thérapie génique, qui comprennent actuellement un essai de phase 1/2 en cours dans l'hémophilie A, et un programme préclinique dans la sclérose latérale amyotrophique (SLA). Suite au transfert de l'IND du giroctocogene fitelparvovec (anciennement SB-525, maintenant PF-07055480), nous avons lancé notre essai de phase 3 évaluant la thérapie génique du giroctocogene fitelparvovec pour le traitement de l'hémophilie A sévère.

L'avenir est ici. En creusant plus profondément, en posant des questions audacieuses et en menant l'innovation scientifique, Pfizer Rare Disease s'efforce d'aller au-delà du contrôle des maladies pour développer des médicaments potentiellement transformateurs et soutenir un mode de vie sain à toutes les étapes de la vie.

Hémophilie

Avant les années 1960, l'espérance de vie moyenne d'un homme atteint d'hémophilie, une maladie de la coagulation sanguine qui provoque des saignements anormaux, était de 12 ans 2 . Aujourd'hui, il s'agit d'une maladie rare traitable, et les patients qui reçoivent un traitement peuvent s'attendre à vivre plus longtemps, en meilleure santé et plus actifs 3 . Pfizer Rare Disease est ancré dans notre héritage et notre engagement envers la communauté de l'hémophilie. Depuis près de trois décennies, nous aidons à soutenir la communauté de l'hémophilie grâce à des ressources et des programmes sur mesure pour amplifier la voix des patients, défendre leurs succès et les soutenir dans certains de leurs plus grands défis. Bien que les options de traitement approuvées fassent de l'hémophilie une maladie gérable, nous croyons qu'il est possible de faire davantage pour faire avancer la science qui contribuera à réaliser les percées de demain.

Amylose à transthyrétine

L'amylose à transthyrétine (ATTR Amylose) est une maladie évolutive rare caractérisée par l'accumulation de dépôts anormaux de protéines amyloïdes composées de protéines transthyrétine mal repliées dans les organes et les tissus du corps 4,5.

Cette maladie peut affecter de nombreuses zones du corps, et les dommages causés par l'accumulation de dépôts amyloïdes sont débilitants et irréversibles, et sont universellement mortels 4,5. Il existe deux présentations de l'amylose ATTR, qui comprennent ATTR-PN et ATTR-CM 6 . Un manque de sensibilisation et de compréhension de l'amylose ATTR a conduit à de faibles taux de diagnostic, et il existe des options de traitement limitées disponibles pour ceux qui sont finalement diagnostiqués 7,8,9.

Pfizer Rare Disease est à l'avant-garde de l'avancement des soins aux personnes atteintes d'amylose ATTR et de l'amélioration de la sensibilisation et de la compréhension de la maladie. Notre recherche aide à mieux comprendre les premiers signes et symptômes, l'épidémiologie et la progression de la maladie, et le fardeau de la maladie pour les patients et les soignants.

Actuellement, Pfizer se concentre sur deux présentations spécifiques de la maladie :

  • Cardiomyopathie amyloïde à transthyrétine (ATTR-CM) : Dans l'ATTR-CM, l'accumulation d'amyloïde se produit principalement dans le cœur et entraîne une cardiomyopathie restrictive et une insuffisance cardiaque progressive 10 . Cette présentation de la maladie peut être héréditaire ou peut être associée au vieillissement 5,11 .
  • Polyneuropathie amyloïde à transthyrétine (ATTR-PN): ATTR-PN résulte d'une mutation génétique du gène de la transthyrétine, lorsque des fibrilles amyloïdes se forment dans les nerfs périphériques et autonomes 12,13.

Dans le cadre de notre engagement, Pfizer Rare Disease mène des recherches en cours sur l'amylose ATTR et soutient la Transthyretin Amyloidosis Outcomes Survey (THAOS), la plus grande base de données internationale en cours et réelle sur l'amylose ATTR. THAOS collecte des données sur les patients atteints d'amylose ATTR, y compris les maladies héréditaires et de type sauvage, et les patients asymptomatiques présentant des mutations TTR, afin d'améliorer la connaissance, la compréhension et la prise en charge de la maladie chez les personnes atteintes de cette maladie.

Dystrophie musculaire de Duchenne

La dystrophie musculaire de Duchenne (DMD) est une maladie génétique infantile rare, grave et débilitante caractérisée par une dégénérescence musculaire progressive qui entraîne des blessures et une faiblesse, et une espérance de vie considérablement raccourcie. La DMD est la forme la plus courante de dystrophie musculaire dans le monde et touche principalement les garçons 14 . Il est urgent de faire progresser la recherche sur la DMD car les options thérapeutiques disponibles sont limitées 15 .

La DMD est un domaine prioritaire de la recherche clinique pour les maladies rares de Pfizer et nous étudions actuellement la thérapie génique comme une option potentielle pour traiter la cause sous-jacente de la maladie.

Travaille avec nous

Si vous êtes intéressé à collaborer avec notre équipe de recherche sur les maladies rares et souhaitez en savoir plus sur notre travail, visitez notre page de partenariat sur les maladies rares. Nous sommes heureux d'avoir l'occasion de discuter de la façon dont nous pouvons travailler ensemble.

Notre focus sur les maladies rares -

Les références:

1. Gènes mondiaux. Faits rares. https://globalgenes.org/rare-facts/. Consulté le 10 février 2020.

2. Organisation nationale des maladies rares. Hémophilie B. https://rarediseases.org/rare-diseases/hemophilia-b/. Consulté le 10 février 2020.

3. Franchini M, Mannucci P. Passé, présent et avenir de l'hémophilie : un examen narratif. Orphanet J Rare Dis. 2012 (7) : 24.

4. Ruberg FL, Berk JL. Amylose cardiaque à transthyrétine (TTR). Circulation. 2012126(10) :1286-1300.

5. Ando Y, Coelho T, Berk JL, et al. Ligne directrice sur l'amylose héréditaire liée à la transthyrétine pour les cliniciens. Orphanet J de Rare Dis. 2013(8) : 31.

6. Stewart M, Alvir J, Cicchetti M, et al. Caractérisation de la charge de morbidité élevée de l'amylose à transthyrétine pour les patients et les soignants. Neurol Ther. 20187(2) :349-364.

7. Rapezzi C, Lorenzini M, Longhi S, et al. Amylose cardiaque : le grand prétendant. Échec cardiaque Rév. 201520(2):117-124.

8. Shirota Y, Iwata A, Ishiura H, et al. Un cas de polyneuropathie amyloïde atypique avec une atteinte prédominante des membres supérieurs avec un diagnostic trouvé de manière inattendue lors d'une opération pulmonaire. Stagiaire Méd. 2010(49):1627-1631.

9. Pareyson D. Diagnostic des neuropathies héréditaires chez les patients adultes. Neurologie. 2003(250):148-160

10. Siddiqi OK, Ruberg FL. Amylose cardiaque : une mise à jour sur la physiopathologie, le diagnostic et le traitement. Tendances Cardiovasc Med. 20171050-1738.

11. Swiecicki PL, Zhen DB, Mauermann ML et al. Amylose ATTR héréditaire : une expérience en établissement unique avec 266 patients. Amyloïde. 201522(2) :123-131.

12. Benson MD, Kincaid JC. La biologie moléculaire et les caractéristiques cliniques de la neuropathie amyloïde. Nerf musculaire. 2007(36):411-423.

13. Hou X, Aguilar M-I, Petit DH. Transthyrétine et polyneuropathie amyloïdotique familiale : progrès récents dans la compréhension du mécanisme moléculaire de la neurodégénérescence. FEBS J. 2007(274):1637-1650.


Valeur de l'indice Copernicus : 97,21

International Journal of Collaborative Research on Internal Medicine & Public Health (IJCRIMPH) est un journal en ligne à comité de lecture en libre accès et une publication interdisciplinaire pour la discussion et le débat collaboratifs sur les questions internationales de médecine interne et de santé publique. La revue promeut des discussions, des études, des recherches collaboratives et des activités en cours sur les sujets actuels de médecine interne et de santé publique, en mettant l'accent sur les études épidémiologiques, les mesures prophylactiques et les méthodes de traitement secondaire et publie des éditoriaux de haute qualité, des articles de recherche, des critiques, des critiques de livres, des rapports de cas, rapports de réunion, articles de méthodologie et rapports succincts.

Ce scientifique publie tous les sujets pertinents dans tous les domaines de la médecine interne comme la médecine de l'adolescence, les maladies cardiovasculaires, la médecine de soins intensifs, l'endocrinologie, le diabète et le métabolisme, la gastro-entérologie, l'hématologie et l'oncologie, les maladies infectieuses, la cardiologie interventionnelle, la néphrologie, les maladies pulmonaires, l'endocrinologie pédiatrique, la rhumatologie , Hépatologie de transplantation, Gestion de l'obésité et du poids, Gestion de la douleur, Sécurité des patients, Maladies rares, Vaccination, Essais cliniques, Déclaration des événements indésirables médicamenteux, Médecine du sport, etc.

Bien que plusieurs sujets importants soient mentionnés, mais la revue ne limitera pas la considération pour la publication, d'autres sujets connexes seront pris en compte s'ils sont jugés appropriés dans le cadre du large champ d'application de la revue.

Les auteurs sont encouragés à partager leurs idées et leurs précieux résultats de recherche via cette plate-forme et à fournir aux lecteurs du monde entier des informations actualisées et les plus importantes à cet égard.

La revue utilise Editor Manager System pour une soumission bien ordonnée à la publication fonctionnant pour les auteurs, les relecteurs et les éditeurs.

Médecine du sport

La médecine du sport est définie comme un domaine de la médecine qui comprend la science de la nutrition et du conditionnement sportifs et pour prévenir et diagnostiquer les blessures sportives et autres problèmes de santé qui affectent les personnes qui pratiquent un sport. Il s'intéresse au fonctionnement du corps humain pendant l'activité physique.

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Médecine translationnelle, Journal of Bioterrorism & Biodefense, Biology and Medicine, Sports Medicine & Doping Studies, American Journal of Sports Medicine, Sports Medicine, British Journal of Sports Medicine, International Journal of Sports Medicine, Clinics in Sports Medicine

Endocrinologie pédiatrique

L'endocrinologie pédiatrique est une sous-spécialité médicale qui traite des variations de la croissance physique et du développement sexuel chez les enfants, du diabète et d'autres troubles des glandes endocrines. Un endocrinologue est un médecin spécialement formé qui a également une formation en médecine interne. Ils diagnostiquent et traitent le déséquilibre hormonal des hormones dans le corps. Les traitements comprennent les problèmes de croissance, la puberté précoce ou retardée, le diabète, l'hypoglycémie, l'obésité, les dysfonctionnements ovariens et testiculaires, etc.

Revues connexes d'endocrinologie pédiatrique

Journal of Proteomics & Bioinformatique, Urologie médicale et chirurgicale, Gynécologie et obstétrique, Journal of Forensic Research, Acta Paediatrica, International Journal of Paediatrics, Recherche hormonale en pédiatrie, Épidémiologie pédiatrique et périnatale, Anesthésie pédiatrique

Obésité et gestion du poids

L'obésité et la gestion du poids sont la mesure du poids en kilogrammes divisé par le carré de la taille en mètres. Il est généralement utilisé pour voir si les adultes ont un poids santé ou une insuffisance pondérale, un surpoids ou une obésité. Être en surpoids ou obèse augmente considérablement le risque de maladies débilitantes multiples, notamment les maladies cardiovasculaires, l'arthrite, l'hypertension artérielle, etc.

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Déclaration des événements indésirables médicamenteux

Un rapport d'événement indésirable médicamenteux est défini comme une équipe de pharmacovigilance qui reçoit des appels concernant les effets indésirables médicamenteux et les enquête. Si un médicament ou un vaccin est d'abord enregistré et mis à disposition, les informations sur son innocuité et son efficacité ne sont disponibles que dans les essais cliniques.

Journaux associés à la déclaration des événements indésirables médicamenteux

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Immunisation

L'immunisation est définie comme le processus par lequel une personne est rendue immunisée ou résistante à une maladie infectieuse, par l'administration d'un vaccin. Les vaccinations sont importantes pour les adultes comme pour les enfants. Les vaccins protègent la personne contre les maladies infectieuses en stimulant le système immunitaire du corps.

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Hépatologie de transplantation

L'hépatologie de transplantation est la branche de la médecine qui s'occupe de l'étude du foie, de la vésicule biliaire, du pancréas et de leurs troubles. L'herpétologue de transplantation travaille avec les chirurgiens de transplantation dans la sélection et la prise en charge des receveurs et des donneurs de greffe du foie. Les hépatologues en transplantation ont une formation complète en hépatologie de transplantation, en maladies infectieuses de transplantation, en hépatopathologie et en radiologie interventionnelle ainsi qu'une formation en recherche avec des compétences cliniques avancées.

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Maladies rares

Une maladie ou un trouble rare est défini comme rare en Europe et peut n'affecter qu'une poignée de patients. 80% des maladies rares sont d'origine génétique, et sont souvent chroniques et mettent la vie en danger. La plupart des maladies rares n'ont pas de remède, donc vivre avec une maladie rare est une expérience continue pour les patients.

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Journal of Clinical Research & Bioethics, Endocrinology & Metabolic Syndrome, Journal of Pharmacogenomics & Pharmacoproteomics, Journal of Medical Diagnostic Methods, Journal of Rare Disorders: Diagnosis & Therapy, Orphanet Journal of Rare Diseases, Chronic Diseases in Canada

Oncologie

L'oncologie est une branche de la médecine qui aide à traiter les tumeurs. Un oncologue est un médecin spécialiste spécialisé en oncologie. Les trois principaux types d'oncologues sont les oncologues médicaux, chirurgicaux et radio-oncologues.

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Médecine générale : libre accès, chimie des produits naturels et recherche, Journal of Molecular Pharmaceutics et recherche sur les processus organiques, médecine alternative et intégrative, Journal of Arthritis, médecine d'urgence : libre accès, Journal of Novel Physiotherapies, Vitamins & Minerals, Journal of Clinical Oncology, Lancet Oncology, International Journal of Radiation Oncology Biologie Physique, Annals of Oncology, Annals of Surgical Oncology, Gynecologic Oncology, Radiotherapy and Oncology, International Journal of Oncology, Critical Reviews in Oncology/Hematology, Journal of Neuro-Oncology

Maladie pulmonaire

La maladie pulmonaire, également connue sous le nom de maladie pulmonaire obstructive chronique, est une maladie évolutive qui rend la respiration difficile. Il existe deux principales formes de bronchopneumopathie chronique obstructive, la bronchite chronique, l'emphysème. Les symptômes comprennent des difficultés respiratoires, de la toux, une respiration sifflante et la production d'expectorations.

Revues connexes de Maladie pulmonaire
International Journal of Physical Medicine & Rehabilitation, Oral Health and Dental Management, International Journal of Emergency Mental Health and Human Resilience, Journal of Pediatric Neurology and Medicine, Current Opinion in Pulmonary Medicine, Pulmonary Pharmacology and Therapeutics, Journal of Cardiopulmonaire Rehabilitation and Prevention, COPD : Journal of Chronic Obstructive Pulmonary Disease, BMC Pulmonary Medicine, Clinical Pulmonary Medicine, Pulmonary Medicine

Médecine des adolescents

La médecine de l'adolescence se concentre sur la promotion du bien-être physique et émotionnel des adolescents. Les spécialistes en médecine de l'adolescence sont les médecins ou autres professionnels de la santé qui s'occupent de jeunes cherchant de l'aide pour des troubles de l'alimentation, des médicaments, des changements d'humeur, des troubles du développement, des problèmes d'identité sexuelle, etc.

Revues connexes de médecine de l'adolescence

Journal of Forensic Medicine, Pediatric Emergency care and medicine- Open Access, Herbal Medicine: Open Access, Journal of Pharmaceutical Care & Health Systems, Adolescent Medicine: State of the Art Reviews, International Journal of Adolescent Medicine and Health, Pediatric and Adolescent Medicine

Cardiologie Interventionnelle

La cardiologie interventionnelle est une branche de la cardiologie qui traite du traitement des maladies cardiaques structurelles. Un cardiologue interventionnel fait référence à diverses procédures non chirurgicales pour traiter les maladies cardiovasculaires telles que l'angine de poitrine et les maladies coronariennes.

Revues connexes de cardiologie interventionnelle

JBR Journal of Interdisciplinaire Medicine and Dental Science, Biology and Medicine, Tropical Medicine & Surgery, Journal of Pharmacovigilance, Journal of the American College of Cardiology, American Journal of Cardiology, Journal of Molecular and Cellular Cardiology, International Journal of Cardiology, Basic Research in Cardiologie, Nature Reviews Cardiology, European Journal of Preventive Cardiology, Opinion actuelle en cardiologie

Médecine de soins intensifs

La médecine de soins intensifs est la spécialité des soins de santé qui aide les personnes atteintes de maladies et de blessures potentiellement mortelles. Il s'adresse aux spécialistes qui traitent les patients, notamment les chirurgiens, les pédiatres, les pharmaciens, les pneumologues, etc.

Revues connexes de médecine de soins intensifs
Alternative & Integrative Medicine, Journal of Molecular Pharmaceutics & Organic Process Research, Natural Products Chemistry & Research, General Medicine: Open Access, American Journal of Respiratory and Critical Care Medicine, Critical Care Medicine, Pediatric Critical Care Medicine, Seminars in Respiratory and Critical Care Medicine, Critical Care Medicine, Pediatric Critical Care Medicine, Seminars in Respiratory and Critical Care Medicine Médecine, soins intensifs et réanimation : journal de l'Australasian Academy of Critical Care Medicine, Indian Journal of Critical Care Medicine, Open Critical Care Medicine Journal

Endocrinologie, diabète & métabolisme

Endocrinologie, diabète et métabolisme fournit une expertise dans les troubles endocriniens, y compris les maladies surrénales, la thyroïde, l'obésité, l'hypophyse, etc. Un endocrinologue est un médecin spécialisé dans le traitement des troubles du système endocrinien et bien d'autres.

Revues connexes d'endocrinologie, du diabète et du métabolisme des amplis
International Journal of Physical Medicine & Rehabilitation, Alternative & Integrative Medicine, Journal of Molecular Pharmaceutics & Organic Process Research, Natural Products Chemistry & Research, Journal of Clinical Endocrinology and Metabolism, Endocrinology, Molecular Endocrinology, American Journal of Physiology - Endocrinology and Metabolism, Diabetes Soins, diabète, recherche et examens sur le diabète/métabolisme, diabète, obésité et métabolisme, recherche sur le diabète et pratique clinique, diabète et métabolisme

Gastroentérologie

La gastro-entérologie est une branche de la médecine qui traite de l'étude des maladies de l'estomac, de l'intestin grêle, du pancréas, du côlon et du rectum, de la vésicule biliaire, des voies biliaires, etc. Un gastro-entérologue est un médecin expérimenté dans la gestion des troubles de l'estomac. et l'intestin.

Revues connexes de gastroentérologie

Journal of Forensic Research, Gynecology & Obstetrics, Medical & Surgical Urology, Journal of Proteomics & Bioinformatics, Gastroenterology, American Journal of Gastroenterology, Clinical Gastroenterology and Hepatology, World Journal of Gastroenterology, Journal of Pediatric Gastroenterology and Nutrition, Journal of Gastroenterology and Hepatology, Journal scandinave de gastroentérologie, Journal européen de gastroentérologie et d'hépatologie, Journal de gastroentérologie clinique, Journal de gastroentérologie

Hématologie

L'hématologie s'occupe de l'étude, du diagnostic, du traitement et de la prévention du sang, des organes hématopoïétiques et des maladies du sang. Les spécialistes traitent des troubles sanguins allant de l'anémie au cancer du sang. Certaines des maladies traitées par des spécialistes comprennent l'anémie ferriprive, la transfusion sanguine, la polyglobulie, la myélofibrose, la leucémie, etc.

Revues connexes d'hématologie
Urologie médicale et chirurgicale, gynécologie et obstétrique, Journal of Health & Medical Informatics, Journal of Nuclear Medicine & Radiation Therapy, Experimental Hematology, Critical Reviews in Oncology/Hematology, Seminars in Hematology, Current Opinion in Hematology, American Journal of Hematology, Hematology/ Cliniques d'oncologie d'Amérique du Nord, Annals of Hematology, Journal of Pediatric Hematology/Oncology, International Journal of Hematology


Comment la MCJ se transmet-elle?

La MCJ ne peut pas être transmise par voie aérienne ou par contact ou par la plupart des autres formes de contact occasionnel. Les conjoints et autres membres de la famille des personnes atteintes de MCJ sporadique n'ont pas un risque plus élevé de contracter la maladie que la population générale. Cependant, l'exposition au tissu cérébral et au liquide médullaire provenant de personnes infectées doit être évitée afin d'empêcher la transmission de la maladie par ces matériaux.

Dans certains cas, la MCJ s'est propagée à d'autres personnes à partir de greffes de dure-mère (un tissu qui recouvre le cerveau), de cornées transplantées, de l'implantation d'électrodes insuffisamment stérilisées dans le cerveau et d'injections d'hormone de croissance hypophysaire contaminée dérivée d'hypophyses humaines prélevées sur cadavres. Les médecins appellent ces cas liés à des procédures médicales iatrogène cas. Depuis 1985, toute l'hormone de croissance humaine utilisée aux États-Unis a été synthétisée par des procédures d'ADN recombinant, ce qui élimine le risque de transmission de la MCJ par cette voie.

De nombreuses personnes craignent qu'il soit possible de transmettre la MCJ par le sang et les produits sanguins apparentés tels que le plasma. Certaines études animales suggèrent que le sang contaminé et les produits apparentés peuvent transmettre la maladie, bien que cela n'ait jamais été démontré chez l'homme. Recent studies suggest that while there may be prions in the blood of individuals with vCJD, this is not the case in individuals with sporadic CJD. Scientists do not know how many abnormal prions a person must receive before he or she develops CJD, so they do not know whether these fluids are potentially infectious or not. They do know that, even though millions of people receive blood transfusions each year, there are no reported cases of someone contracting sporadic CJD from a transfusion. Even among people with hemophilia (a rare bleeding disorder in which the blood does not clot normally), who sometimes receive blood plasma concentrated from thousands of donors, there are no reported cases of CJD.

While there is no evidence that blood from people with sporadic CJD is infectious, studies have found that infectious prions from BSE and vCJD accumulate in the lymph nodes (which produce white blood cells), the spleen, and the tonsils. At present, four cases of vCJD infection have been identified following transfusion of red blood cells from asymptomatic donors who subsequently died from vCJD. Recently, one case of likely transmission of vCJD infection by concentrates of blood-clotting protein has been reported in an elderly individual with hemophilia in the United Kingdom. The possibility that blood from people with vCJD may be infectious has led to a policy preventing individuals in the United States from donating blood if they have resided for more than three months in a country or countries where BSE is common.

Both brain biopsy and autopsy pose a small, but definite, risk that the surgeon or others who handle the brain tissue may become accidentally infected by self-inoculation.

Special surgical and disinfection procedures can markedly reduce this risk. A fact sheet with guidance on these procedures is available from the National Institute of Neurological Disorders and Stroke (NINDS) and the World Health Organization.


Discussion

SCI affects a patient’s physical, social, and psychological well-being and places a substantial burden on health care systems, families, and communities. An understanding of the prevalence and incidence of SCI enables health care systems to implement preventative strategies and allocate resources appropriately for disease management. In addition, by observing trends in SCI incidence over time, such as the decrease seen in Spain or the increase in the United States, systems can gather feedback as to what preventative measures have worked.

Based on this review, we have identified nine studies that have reported on the prevalence and 44 studies that have discussed the incidence of acute SCI. The prevalence of SCI was the highest in the United States of America (906 per million) and the lowest in the Rhone-Alpes region, France (250 per million) and Helsinki, Finland (280 per million). With respect to states and provinces, the incidence of SCI was the highest in Alaska (83 per million) and Mississippi (77 per million) and the lowest in Alabama (29.4 per million), despite a large percentage of violence injuries (21.2%). Incidences were above 50 per million in Hualien County in Taiwan (56.1 per million), the central Portugal region (58 per million), and Olmsted County in Minnesota (54.8 per million) and were lower than 20 per million in Taipei, Taiwan (14.6 per million), the Rhone-Alpes region in France (12.7 per million), Aragon, Spain (12.1 per million), Southeast Turkey (16.9 per million), and Stockholm, Sweden (19.5 per million). The highest national incidence was 49.1 per million in New Zealand, and the lowest incidence was in Fiji (10.0 per million) and Spain (1984�: 8.0 per million). The majority of studies showed a high male-to-female ratio and an age of peak incidence of younger than 30 years old. Traffic accidents were typically the most common cause of SCI, followed by falls in the elderly population.

As the population ages, it is important to observe trends in the age of peak incidence, as this may change. Currently, in most regions and countries, a larger percentage of SCI patients are under the age of 30. One of the exceptions to this trend was in Japan, where the majority of the patients sustaining SCIs were over the age of 50 years.52 This is primarily due to early spinal degenerative changes, specifically OPLL, as well as an increased prevalence of congenital stenosis, causing a higher risk of SCI following a traumatic event.58 Degeneration of various components of the vertebra is common in the elderly population and may lead to narrowing of the spinal canal.59 In turn, these degenerative changes place people at a greater risk of suffering SCI following a fall or another traumatic event.58 Therefore, with the aging of the population, acute care systems may be confronted with an increased number of elderly patients with SCI and should plan and allocate resources accordingly.59

The rates of SCIs vary across countries, regions, and cities. This could be a reflection of actual differences in incidence or a result of differences in case ascertainment. For example, some studies have used information from death certificates, coroners, or the department of legal medicine to include SCI victims who have died at the scene of the accident or during transport to acute care centers. Other studies have excluded these patients from their estimates. In addition, identification of patients with acute SCI was done in different ways across studies. Some used ICD-9 or ICD-10 codes to detect relevant patients, whereas others used a simple clinical definition, surveys, or questionnaires. In order to make comparisons between countries or to accurately estimate global incidence, methodologies of data collection must be standardized.

It is also challenging to compare differences in SCI causation across countries due to a lack of standard definitions. For example, some studies have defined motor vehicle accidents as any collision involving a motorized vehicle, including hitting a pedestrian or cyclist, whereas other studies have separated accidents involving pedestrians into a separate category. Another example is sport injuries: some studies have combined diving and other sporting activities into a single category, while others have divided these two into separate categories. In this review, we have attempted to standardize these definitions in order to make comparisons.

This review summarizes what is currently known in the literature on the incidence and prevalence of SCI.


Neurology Basic and Translational Research Programs and Laboratories

We are interested in understanding how immune responses promote neurological disease. Recent advances in human genetics, particularly for neurodegenerative disorders like Alzheimer’s disease, have highlighted a causal role of disrupted immune responses in disease pathogenesis. An injurious immune response may be a common denominator across many neurological disorders, both acute (brain trauma or stroke) and chronic (epilepsy, Parkinson’s disease, Alzheimer's for eg.). An understanding of how innate immune responses cause neurological disease will be essential if we are to develop disease-modifying therapies for our patients. Using systems biology approaches, we are identifying immune pathways that regulate immune metabolism and immune responses at the brain interface. Our objectives are (1) to understand how aberrant brain and/or peripheral innate immune responses cause synapse loss and contribute to the vulnerability of selected circuits in different neurologic disorders, and (2) to develop preventive and therapeutic strategies targeting these inflammatory pathways in patients with neurologic diseases.

Baumer Lab

Within the Department of Neurology at Stanford University, Fiona Baumer's lab aims to better understand the relationship between various forms of pediatric epilepsy, cognition and learning.

We specifically research benign rolandic epilepsy (BECTs) and absence epilepsy. We hope to better understand how differences in brain excitation, plasticity and connectivity relate to difficulty with language, attention and learning in these conditions.

Bronte-Stewart Lab

The Bronte-Stewart Lab investigates the brain’s contribution to abnormal movement in human subjects, using synchronous brain recordings and quantitative kinematics, and how these are modulated with different frequencies and patterns of neurostimulation. Dr. Bronte-Stewart’s team was the first in the United States to implant a sensing neurostimulator and now have the largest cohort of implanted patients in the world. From these devices, they can record brain signals directly, and use the patient’s own neural activity to drive the first closed loop neurostimulation studies in Parkinson’s disease. This work has led to the first multicenter national clinical trial in closed loop deep brain stimulation for people with Parkinson’s disease, which Dr. Bronte-Stewart will lead. Other clinical trials conducted include a study of the neurodegeneration in HIV infection and the safety of young plasma infusions as a potential treatment for Parkinson's disease.

Buckwalter Lab

The Buckwalter lab studies how inflammatory responses after brain injury affect neurological recovery.

Day Lab

The Day Lab focuses on defining the central nervous system features of neuromuscular disorders, which severely impact patients and families but have been incompletely investigated, explained or managed. Detailed neuropsychological and brain MRI studies help define the developmental and progressive CNS aspects of these conditions, for which we then seek molecular and cellular explanations through cell-based studies of patient-derived specimens. To assure our research is translatable to clinical practice, we are simultaneously involved in collaborative clinical research on novel treatments for neuromuscular disease, including antisense oligonucleotides and pharmacologic manipulation of muscle function, viral gene therapies and cell-based treatments.

Jun Ding Lab

The Ding lab uses interdisciplinary approaches to dissect the functional organization of motor circuits, particularly cortico-thalamo-basal ganglia networks. The long-term scientific goal of the Ding Lab is to construct functional circuit diagrams and establish causal relationships between activity in specific groups of neurons, circuit function, animal motor behavior and motor learing, and, thereby, to decipher how the basal ganglia process information and guide motor behavior. In addition, we aim to further help construct the details of psychomotor disorder 'circuit diagrams,' such as changes in Parkinson's disease, drug abuse and addiction.

George Lab

The George lab applies bioengineering approaches to explore neurological disorders. Our particular focus is utilizing interactive biomaterials to promote neural recovery. Through the use of biomaterials, microfabrication techniques, and stem cell therapeutics, we are able to manipulate the neural environment and determine important pathways for healing. Our goal is to use these pathways to develop new treatments for patients with stroke and other neurological diseases. With nearly 800,000 strokes occurring annually in the United States alone, stroke remains a leading cause of long term disability and death in the world. Despite stroke’s prevalence, currently there are no medical therapies to improve subacute and chronic stroke recovery. The George lab strives to increase our understanding of naturally occurring repair mechanisms through biomarkers and novel technologies to improve the care of stroke survivors.

Greicius Lab (Functional Imaging in Neuropsychiatric Disorders)

The Greicius lab uses imaging, genetics, and imaging genetics to better understand Alzheimer’s disease and related disorders from the level of molecular pathways to large-scale distributed brain networks and behavior. Recent and ongoing work leverages the APOE4 genetic variation that increases risk for Alzheimer’s disease. In the Stanford Extreme Phenotypes in Alzheimer’s Disease (StEP AD) study, the lab is looking for protective genetic variants in healthy older subjects that have 1 or 2 copies of the high-risk APOE4 gene but do not show signs of Alzheimer’s disease. The StEP AD study is also looking at the for novel causal genetic mutations in patients with early-onset Alzheimer’s disease who do not have the APOE4 variant. All participants undergo “deep phenotyping” including molecular imaging, immunophenotyping, and blood/spinal fluid biomarkers. The expectation is that novel protective or causal variants identified in the StEP AD study will provide novel targets for drug development.

Han Lab

Research in the Han lab mainly focuses on Multiple Sclerosis (MS) and other inflammatory demyelinating diseases of the CNS. Our goal is to identify biomarkers to monitor disease activity and to understand protective molecules that are present during neuroinflammation.

We are a translational research lab, thus we strive to directly apply our knowledge from bench to bedside. We study patient samples utilizing Systems Biology approach. We test our hypothesis in animal models, cellular and biochemical assays to decipher the molecular mechanism with the ultimate goal to apply the knowledge directly to patient care.

Henderson Lab

Within the population health sciences, our research agenda encompasses cognitive change that occurs as a usual concomitant of normal aging and the debilitating cognitive impairment that accompanies Alzheimer’s disease and other forms of dementia. Pathological changes of Alzheimer’s disease are believed to begin years, if not decades, before the onset of mental symptoms. For this reason, a key aspect of our research includes the investigation of factors that affect cognitive skills at midlife, a time when therapeutic interventions offer the greatest potential of forestalling late-life impairment. Our approach includes both investigator-initiated randomized clinical trials and population-based observational research. One important platform for our work is the Stanford Alzheimer’s Disease Research Center, a congressionally-mandated NIH center of excellence funded by the National Institute on Aging. We have also partnered with clinical epidemiologists at the University of Aarhus, Denmark, to examine risk factors for Alzheimer’s disease using linked Danish medical registries.

Huang Lab

The Huang Lab studies the role of oxygen free radicals in oxidative tissue damage and degeneration. Our research tools include transgenic and knockout mice and tissue culture cells for in vitro gene expression.

Our research focuses on the role of redox balance in tissue maintenance and repair. Under normal metabolic conditions, oxygen free radicals are generated as by-products from oxidative phosphorylation in the mitochondria and from normal biochemical reactions in the cytosol. Oxygen free radicals are highly reactive, hence the name reactive oxygen species (ROS), and can cause damages to macromolecules, such as DNA, RNA, lipids, and proteins.

Huguenard Lab

We are interested in the neuronal mechanisms that underlie synchronous oscillatory activity in the thalamus, cortex and the massively interconnected thalamocortical system. Such oscillations are related to cognitive processes, normal sleep activities and certain forms of epilepsy. Our approach is an analysis of the discrete components that make up thalamic and cortical circuits, and reconstitution of components into both in vitro biological and in silico computational networks. Accordingly, we have been able to identify genes whose products, mainly ion channels, play key roles in the regulation of thalamocortical network responses. Using this knowledge we have recently designed targeted optogenetic approaches to detect seizures at their onset, and then in real time disrupt them by instantly modifying the activity of key elements in the epileptic circuit.

James Lab

The primary aim of the James Lab is to improve the diagnosis and treatment of brain diseases by developing translational molecular imaging agents for visualizing neuroimmune interactions underlying conditions such as Alzheimer’s disease, multiple sclerosis, and stroke. We are researching how the brain and its resident immune cells interact with the peripheral immune system at very early, through to late, stages of disease. Our approach involves the discovery and characterization of clinically relevant immune cell biomarkers, followed by the design of imaging agents specifically targeting these biomarkers. After preclinical validation, we translate promising imaging probes to the clinic to enable precision targeting of immunomodulatory therapeutics and real-time monitoring of treatment response.

Lee Lab

The Lee Lab uses interdisciplinary approaches from biology and engineering to analyze, debug, and manipulate systems-level brain circuits. We seek to understand the connectivity and function of these large-scale networks in order to drive the development of new therapies for neurological diseases. This research finds its basic building blocks in areas ranging from medical imaging and signal processing to genetics and molecular biology.

Longo Lab

Dr. Longo and his research team are focused on elucidating mechanisms underlying neurodegenerative disorders and developing small molecule therapeutic strategies that target these mechanisms. Neurotrophin proteins bind to multiple receptors (p75, TrkA-C) to modulate survival, functional and degenerative intracellular signaling and synaptic function. The Longo laboratory and collaborators pioneered the mechanistic principle that non-peptide small molecules targeting individual receptor epitopes can activate or modulate neurotrophin receptors to produce distinctive biological effects capable of inhibiting disease mechanisms. This work has led to successful efficacy trials in many mouse models of neurodegenerative disorders including Alzheimer’s, Huntington’s, and Parkinson’s diseases as well as spinal cord injury, traumatic brain injury, chemotherapy-induced neuropathy, ischemic stroke recovery, Rett syndrome, and epilepsy. One of our small molecules, the p75 NTR ligand, LM11A-31, has progressed through a human phase 1 safety trial and is in a phase 2a Alzheimer’s disease trial ongoing in Europe. We have been fortunate to execute the rare full translational spectrum of: identifying novel basic mechanisms, creating novel entities to target those mechanisms, moving these therapeutic candidates through mouse and other pre-clinical studies, progressing one of these candidates to first-in-human safety studies and testing of the first-in-class therapeutic entity in neurodegenerative disease subjects.


Growing hope: New organs? Not yet, but stem cell research is getting closer

Kidney (Image by Lori O'Brien/Andy McMahon Lab, illustration by Mira Nameth)

If you lose a limb, it’s lost for life. If you damage a kidney, you won’t grow a new one. And if you have a heart attack, the scars are there to stay.

But regenerative medicine is poised to change all of this. Building new tissue is within sight, and USC scientists are among the field’s pioneers.

More than 100 scientists, engineers and doctors are united under what’s called the USC Stem Cell initiative. They’re already moving stem cells out of the lab and toward patient care. The potential is exciting: USC researchers have contributed to clinical trials of stem cell approaches to treating colorectal cancer, spinal cord injury, vision problems, HIV/AIDS and Alzheimer’s disease. They’ve also used stem cells to uncover important insights about kidney disease, ALS, arthritis, Zika virus, birth defects and a wide variety of injuries.

Major funders and USC donors have provided hundreds of millions of dollars to support the work. That investment and vote of confidence enables USC Stem Cell scientists to collaborate with other leading universities, biotech companies and key partners to translate their laboratory discoveries into patient cures.

It hasn’t been easy. Scientists are evaluating some stem cell-based therapies through clinical trials, but so far, few treatments have made it to patients. Beyond scientific inspiration, taking treatments from lab bench to patient bedside requires immense amounts of time, money and, sometimes, a bit of luck. It also means working together with other scientists across boundaries.

“Regenerative medicine is still a relatively young field, and it’s still early days,” says Andy McMahon, director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. “When it comes to that final phase of translating stem cell discoveries into clinical therapies for patients, it won’t be individual universities working in isolation. It will be multi-institutional collaborations with our neighbors that will transform medicine over the course of the 21st century.”

The Kidney in Miniature

So far, scientists haven’t been able to create complete adult human kidneys—they’re too complex.

At USC, though, McMahon’s lab is coaxing stem cells to organize themselves into simplified, mini versions of this elaborate organ.

Each healthy human kidney is made up of a million cellular filters called nephrons, which pull wastes out of blood, among other responsibilities. McMahon and his colleagues are making tiny organs (scientists dub them “organoids”) composed of a single nephron—a convenient size for testing potential drugs.

With help from USC’s Chang Stem Cell Engineering Facility, McMahon’s lab has successfully produced organoids carrying the same genetic mutation that causes polycystic kidney disease, the most common genetic cause for kidney failure. Because kidney organoids develop cysts similar to those seen in the disease, scientists can observe how the disease progresses and develop therapies that may halt or reverse symptoms.

Zhongwei Li, an assistant professor of medicine, and stem cell biology and regenerative medicine, is also hard at work growing kidney organoids. There are only 18,000 donor kidneys available each year for more than 400,000 patients who need them, Li explains. He ultimately wants to create organs for transplantation using special stem cellsprogenitor cells that could develop and organize themselves into kidney tissue.

“USC is a perfect place to study the kidney,” says Li, an assistant professor of medicine, and stem cell biology and regenerative medicine.

Healing Hearts

/>Heart tissue (Image by Megan McCain, illustration by Mira Nameth)

If you worry about dying in an earthquake, shark attack or lightning strike, don’t waste your energy. You’re far more likely to die of heart disease. Every year, about 610,000 people in the U.S. die of heart disease. That’s one in four deaths. And heart disease is the leading cause of death worldwide.

Cardiac tissue that has died after a heart attack doesn’t come back—it just forms a scar. Studies have shown that doctors can safely inject stem cells into damaged heart tissue, but there’s no clear sign that these injections restore the heart.

At USC, two stem cell researchers are tackling heart repair from other directions.

In the lab of Henry Sucov, researchers aim to harness the heart’s innate ability to heal. They’re studying a regenerative type of heart muscle cell called a mononuclear diploid cardiomyocyte. Newborns have large numbers of these cells, but adults have relatively few, so the adult body has trouble regenerating heart tissue after injury.

When they looked for these cells in mice, they found that some mice had more of these cells than other mice did. They traced that variation to a gene called Tnni3k. Their research suggests that blocking the gene might boost numbers of regenerative cells.

If scientists can create prescription drugs to modulate the activity of the gene, these medications could encourage more regenerative cells to develop in the heart, says Sucov, a professor of stem cell biology and regenerative medicine, integrative anatomical sciences, and biochemistry and molecular biology. “This could improve the potential for regeneration in adult hearts, as a preventive strategy for those who may be at risk for heart failure.”

In Megan McCain’s lab at the USC Viterbi School of Engineering, researchers are building human heart tissue. They not only study how the heart tissue works, but also use it to test how it responds to potential drugs.

The work poses problems that call for the mindset of an engineer. It turns out that heart muscle cells don’t fully mature in the typical laboratory environment for growing cells—a petri dish filled with warm, nutritious liquid. To develop properly, heart muscle cells need to get some exercise by contracting in the rhythm of a beating heart. To do this, they need structure and resistance, which the lab’s researchers provide in the form of a tiny scaffold called a chip.

This “heart on a chip” reproduces natural human heart tissue on a small scale in the lab.

Ultimately, McCain hopes the technology contributes to precision medicine. Scientists could test medications on a patient’s own heart tissue on a chip. Eventually, this could enable doctors to customize dosing and choose drugs that pose the fewest side effects to each patient.

Stronger Bones

/>Mouse ribs (Image by Francesca Mariani, illustration by Mira Nameth)

According to common wisdom, bones heal. In reality, every year about 5 million people in the U.S. sustain fractures that fail to mend. From elderly people undergoing total hip or knee replacements to soldiers injured by explosions or gunshots, many patients have bone defects that are too severe to repair. To complicate matters, everything from diabetes to the normal aging process can undermine bone’s ability to heal.

USC researchers hope to one day use stem cells to build new bone in patients with severe or non-healing injuries. Jay R. Lieberman, who chairs the Department of Orthopaedic Surgery at the Keck School, teamed up with Gage Crump and Francesca Mariani, two faculty members from the Department of Stem Cell Biology and Regenerative Medicine, to advance the science.

The team has made a promising start in the lab. They discovered that healing bone requires a special type of repair cell, which they named an ossifying chondrocyte. Now the researchers are studying a substance that stimulates these repair cells to fix bone.

Unlocking Genetic Diabetes

Nearly 10 percent of Americans, or 30 million people, have a form of diabetes. Diabetes happens when glucose levels rise in the blood. Insulin, a hormone made by the pancreas, helps the body pull glucose from blood and into the cells where it’s needed. But sometimes the pancreas doesn’t make enough insulin or the body can’t use insulin well.

Oftentimes, in diabetes, the special cells in the pancreas that make insulin—called beta cells—are attacked by the immune system or wear out. Researchers worldwide are looking at ways to rebuild them.

At Children’s Hospital Los Angeles (CHLA), researcher Senta Georgia aims to use stem cells to help patients with genetic forms of diabetes.

Her lab is focusing on a young CHLA patient with a rare genetic disease known as enteric anendocrinosis. The disease causes chronic diarrhea because patients lack certain gastrointestinal cells that produce hormones, and they eventually lose their beta cells as well, causing diabetes.

With the help of USC’s Chang Stem Cell Engineering Facility, Georgia’s team took stem cells derived from the patient’s skin and edited the cells’ genome to fix the genetic mutation behind the problem. They then used these genetically corrected stem cells to generate new insulin-producing cells.
The goal is to eventually transplant these insulin-producing cells back into the patient to reverse the diabetes—providing a tailor-made cell replacement therapy.

“We hope that this study can create a precedent for how to generate new insulin cells for patients with genetic forms of diabetes,” says Georgia, assistant professor of pediatrics and stem cell biology and regenerative medicine at the Keck School of Medicine of USC.

Fresh Faces

“Our faces are our identities, and the first thing you see when you look at someone is his or her face,” says Yang Chai, director of the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry of USC. But when someone has a cleft lip or other facial deformity or trauma, it can be devastating.

Chai aims to find treatments for some of the most common craniofacial birth defects and injuries. To do that, he has tapped into a rich source of stem cells: the pulpy interior of the teeth.

Fueled by a $12 million grant from the National Institutes of Health (NIH), he’s working with researchers from the Keck School of Medicine and institutions from Stanford to City of Hope on the project.

They’ve already used these stem cells to generate the unique, high-density bone that makes up the skull. If these stem cells can effectively repair four-centimeter holes in the skulls of animals, the research project will advance the treatment into a clinical trial for patients with bone deficiencies due to injuries, dental problems or birth defects.

One birth defect USC scientists are tackling is called craniosynostosis. The rare-but-serious problem occurs when sections of a baby’s skull fuse together at joints called sutures, restricting the developing brain and disrupting vision, sleep, eating and IQ. To treat this condition, growing children must undergo repeated skull-expanding surgeries—which are as dangerous and painful as they sound.

Chai is one of at least a dozen USC stem cell researchers working to help these children. His lab has already identified a critical stem cell population that normally resides in the skull sutures, and discovered how to manipulate these stem cells to form new sutures in mice.

“This is something that truly has to be done through a collaborative effort,” Chai says. “USC provides the best environment for collaborative research, which has led to NIH funding and publications as the result of these collaborations. These collaborative studies will fundamentally change the way to provide health care to our patients.”


Health versus disease

Before human disease can be discussed, the meanings of the terms health, physical fitness, illness, and disease must be considered. Health could be defined theoretically in terms of certain measured values for example, a person having normal body temperature, pulse and breathing rates, blood pressure, height, weight, acuity of vision, sensitivity of hearing, and other normal measurable characteristics might be termed healthy. But what does normal mean, and how is it established? It is well known that if the temperatures are taken of a large number of active, presumably healthy, individuals the temperatures will all come close to 98.6 °F (37 °C). The great preponderance of these values will fall between 98.4 °F (36.9 °C) and 98.8 °F (37.1 °C). Thus, health could in part be defined as having a temperature within this narrow range. Similarly, a normal range can be established for pulse, blood pressure, and height. In some healthy individuals, however, the body temperature may range below 98.4 °F or above 98.8 °F. These low and high temperatures fall outside the limits defined above as normal and are instances of biological variability.

Biological criteria of normality are based on statistical concepts. Body height may be used as an example. If the heights of every individual in a large sample were plotted on a graph, the many points would fall on a bell-shaped curve. At one end of the curve would be the very short people, and at the other extreme the few very tall people. The majority of the points of the sample population would fall on the dome of the bell-shaped curve. At the peak of the dome would be those individuals whose height approaches the average of all the heights. Scientists use curves in determining what they call normal criteria. By accepted statistical criteria, 95 percent of the population measured would be included in the normal range—that is, 47.5 percent above and 47.5 percent below the mean at the very centre of the bell. Looked at in another way, in any given normal biological distribution 5 percent will be considered outside the normal range. Thus the 7-foot (213-cm) basketball player would be considered abnormally tall, but that which is abnormal must be distinguished from that which represents disease. The basketball player might be abnormally tall but still have excellent health. Thus, in any statistical analysis of health, the possibility of biological variation must be recognized.

A better example than height of how problems can arise with biological variability is heart size. If the heart is subjected to a greater than normal burden over a long period, it can respond by growing larger (the process is known as hypertrophy). This occurs in certain forms of heart disease, especially in those involving long-standing high blood pressure or structural defects of the heart valves. A large heart, therefore, may be a sign of disease. On the other hand, it is not uncommon for athletes to have large hearts. Continuous strenuous exercise requires a greater output of blood to the tissues, and the heart adapts to this demand by becoming larger. In some cases the decision as to whether an abnormally large heart represents evidence of disease or is simply a biological variant may tax the diagnostic abilities of the physician.

The effects of age introduce yet another difficulty in the attempt to define health in theoretical measured norms. It is well known that muscular strength diminishes in the advanced years of life, the bones become more delicate and more easily fractured, vision and hearing become less sharp, and a variety of other retrogressive changes occur. There is some basis for considering this general deterioration as a disease, but, in view of the fact that it affects virtually everyone, it can be accepted as normal. Theoretical criteria for health, then, would have to be set for virtually every year of life. Thus, one would have to say that it is normal for a man of 80 to be breathless after climbing two flights of stairs, while such breathlessness would be distinctly abnormal in an agile child of 10 years of age. Moreover, an individual’s general level of physical activity significantly alters his ability to respond to the ordinary demands of daily life. The amount of muscular strength possessed by an 80-year-old man who has remained physically active would be considerably more than that of his fragile friend who has led a confined life because of his dislike of activity. There are, therefore, many difficulties in establishing criteria for health in terms of absolute values.

Health might be defined better as the ability to function effectively in complete harmony with one’s environment. Implied in such a definition is the capability of meeting—physically, emotionally, and mentally—the ordinary stresses of life. In this definition health is interpreted in terms of the individual’s environment. Health to the construction worker would have a dimension different from health to the bookkeeper. The healthy construction worker expects to be able to do manual labour all day, while the bookkeeper, although perfectly capable of performing sedentary work, would be totally incapable of such heavy labour and indeed might collapse from the physical strain yet both individuals might be termed completely healthy in terms of their own way of life.

The term physical fitness, although frequently used, is also exceedingly difficult to define. In general it refers to the state of optimal maintenance of muscular strength, proper function of the internal organs, and youthful vigour. The champion athlete prepared to cope not only with the commonplace stresses of life but also with the unusual illustrates the concept of physical fitness. To be in good physical condition is to have the ability to swim a mile to save one’s life or to slog home through snowdrifts when a car breaks down in a storm. Some experts in fitness insist that the state of health requires that the individual be in prime physical condition. They prefer to divide the spectrum of health and disease into (1) health, (2) absence of disease, and (3) disease. In their view, those who are not in prime condition and are not physically fit cannot be considered as healthy merely because they have no disease.

Health involves more than physical fitness, since it also implies mental and emotional well-being. Should the angry, frustrated, emotionally unstable person in excellent physical condition be called healthy? Certainly this individual could not be characterized as effectively functioning in complete harmony with the environment. Indeed, such an individual is incapable of good judgment and rational response. Health, then, is not merely the absence of illness or disease but involves the ability to function in harmony with one’s environment and to meet the usual and sometimes unusual demands of daily life.

The definitions of illness and disease are equally difficult problems. Despite the fact that these terms are often used interchangeably, illness is not to be equated with disease. A person may have a disease for many years without even being aware of its presence. Although diseased, this person is not ill. Similarly, a person with diabetes who has received adequate insulin treatment is not ill. An individual who has cancer is often totally unaware of having the disorder and is not ill until after many years of growth of the tumour, during which time it has caused no symptoms. The term illness implies discomfort or inability to function optimally. Hence it is a subjective state of lack of well-being produced by disease. Regrettably, many diseases escape detection and possible cure because they remain symptomless for long years before they produce discomfort or impair function.

Disease, which can be defined at the simplest level as any deviation from normal form and function, may either be associated with illness or be latent. In the latter circumstance, the disease will either become apparent at some later time or will render the individual more susceptible to illness. The person who fractures an ankle has an injury—a disease—producing immediate illness. Both form and function have been impaired. The illness occurred at the instant of the development of the injury or disease. The child who is infected with measles, on the other hand, does not become ill until approximately 10 days after exposure (the incubation period). During this incubation period the child is not ill but has a viral infectious disease that is incubating and will soon produce discomfort and illness. Some diseases render a person more susceptible to illness only when the person is under stress. Some diseases may consist of only extremely subtle defects in cells that render the cells more susceptible to injury in certain situations. The blood disease known as sickle cell anemia, for example, results from a hereditary abnormality in the production of the red oxygen-carrying pigment (hemoglobin) of the red cells of the blood. The child of a mother and father who both have sickle cell anemia will probably inherit an overt form of sickle cell anemia and will have the same disease as the parents. If only one parent has sickle cell anemia, however, the child may inherit only a tendency to sickle cell anemia. This tendency is referred to by physicians as the sickle cell trait. Individuals having such a trait are not anemic but have a greater likelihood of developing such a disease. When they climb a mountain and are exposed to lower levels of oxygen in the air, red blood cells are destroyed and anemia develops. This can serve as an example of a disease or a disease trait that renders the affected person more susceptible to illness.

Disease, defined as any deviation from normal form and function, may be trivial if the deviation is minimal. A minor skin infection might be considered trivial, for example. On the eyelid, however, such an infection could produce considerable discomfort or illness. Any departure from the state of health, then, is a disease, whether health be measured in the theoretical terms of normal measured values or in the more pragmatic terms of ability to function effectively in harmony with one’s environment.


De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy

Fond: Profiling the entire genome at base pair resolution in a single test offers novel insights into disease by means of dissection of genetic contributors to phenotypic features.

Méthodes : We performed genome sequencing for a patient who presented with atypical hereditary sensory and autonomic neuropathy, severe epileptic encephalopathy, global developmental delay, and growth hormone deficiency.

Résultats: Assessment of the variants detected by mapped sequencing reads followed by Sanger confirmation revealed that the proband is a compound heterozygote for rare variants within RETREG1 (FAM134B), a gene associated with a recessive form of hereditary sensory and autonomic neuropathy, but not with epileptic encephalopathy or global developmental delay. Further analysis of the data also revealed a heterozygous missense variant in DNM1L, a gene previously implicated in an autosomal dominant encephalopathy, epilepsy, and global developmental delay and confirmed by Sanger sequencing to be a de novo variant not present in parental genomes.

Conclusion : Our findings emphasize the importance of genome-wide sequencing in patients with a well-characterized genetic disease with atypical presentation. This approach reduces the potential for misdiagnoses.

Mots clés: DNM1L HSAN epileptic encephalopathy intradermal histamine test self-injury whole genome sequencing.

© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Déclaration de conflit d'intérêts

All authors declare that they have no conflict of interest or financial relationships that could be considered conflict of interest.


Voir la vidéo: Les maladies rares. Le patient expert (Décembre 2022).