The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
John A Phillips - One of the best experts on this subject based on the ideXlab platform.
-
c type natriuretic peptide analogue therapy in children with achondroplasia
The New England Journal of Medicine, 2019Co-Authors: Ravi Savarirayan, Melita Irving, Carlos A Bacino, Bret L Bostwick, Joel Charrow, Valerie Cormierdaire, Kim Hanh Le Quan Sang, Patricia I Dickson, Paul Harmatz, John A PhillipsAbstract:Abstract Background Achondroplasia is a Genetic Disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosor...
-
dopamine beta hydroxylase deficiency a Genetic Disorder of cardiovascular regulation
Hypertension, 1991Co-Authors: David Robertson, Virginia Haile, S E Perry, R M Robertson, John A Phillips, Italo BiaggioniAbstract:Dopamine beta-hydroxylase (DBH) deficiency is a Genetic Disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one.
Frederick S Kaplan - One of the best experts on this subject based on the ideXlab platform.
-
druggable targets clinical trial design and proposed pharmacological management in fibrodysplasia ossificans progressiva
Expert opinion on orphan drugs, 2020Co-Authors: Robert J Pignolo, Frederick S KaplanAbstract:Introduction: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare Genetic Disorder characterized by heterotopic ossification, congenital skeletal abnormalities especially of the great toes...
-
insights from a rare Genetic Disorder of extra skeletal bone formation fibrodysplasia ossificans progressiva fop
Bone, 2008Co-Authors: Eileen M Shore, Frederick S KaplanAbstract:Fibrodysplasia ossificans progressiva (FOP) is a rare human Genetic Disorder of extensive and debilitating extra-skeletal bone formation. While the challenges of investigating a rare condition are many, the potential benefits are also great - not only for the specific disease under investigation, but also for the unique perspective on how cells normally function and the mechanisms that underlie more common Disorders. This review will illustrate some of the many insights that we have gained by studying FOP.
-
paresis of a bone morphoGenetic protein antagonist response in a Genetic Disorder of heterotopic skeletogenesis
Journal of Bone and Joint Surgery American Volume, 2003Co-Authors: Lourdes Serrano De La Pena, Eileen M Shore, Frederick S KaplanAbstract:Background: Fibrodysplasia ossificans progressiva is a rare Genetic Disorder characterized by congenital malformations of the great toes and by progressive heterotopic bone formation. Bone morphoGenetic protein-4 (BMP-4) messenger ribonucleic acid (mRNA) and protein are uniquely overexpressed in lymphocytes and lesional cells from patients who have fibrodysplasia ossificans progressiva. However, the BMP-4 gene is not mutated in fibrodysplasia ossificans progressiva. The activities of BMPs are specified in part by the formation of morphogen gradients that are further regulated by an array of secreted antagonists. Recent studies have indicated that BMP-4 upregulates the expression of the BMP antagonists noggin, gremlin, and follistatin, thereby establishing an autoregulatory feedback loop. Therefore, a defect in the feedback pathway between BMP-4 and one or more of its extracellular antagonists could contribute to the elevated BMP-4 activity characteristic of fibrodysplasia ossificans progressiva. Methods: Basal and BMP-4-induced expression of noggin, gremlin, follistatin, and chordin mRNA were investigated in control and fibrodysplasia ossificans progressiva lymphoblastoid cell lines with use of reverse transcriptase-polymerase chain reaction and Northern analysis. Results: In the absence of exogenous BMP-4 stimulation (basal state), steady-state levels of all of the BMP antagonists that were investigated were similar in fibrodysplasia ossificans progressiva and control cell lines. Upon stimulation with recombinant human BMP-4, control lymphoblastoid cell lines exhibited a marked increase in expression of noggin and gremlin mRNA. Fibrodysplasia ossificans progressiva cells, however, showed a dramatically attenuated response to BMP-4 stimulation compared with that of controls. Conclusions: These data indicate a paresis of a BMP-antagonist response, suggesting the loss of a negative feedback mechanism by which cells normally regulate the magnitude and boundaries of ambient morphoGenetic signals. This paresis may account in part for the increased BMP-4 activity in fibrodysplasia ossificans progressiva. Clinical Relevance: Our findings suggest the potential usefulness of BMP-antagonist-based strategies in the therapy for patients with fibrodysplasia ossificans progressiva and other Disorders of excessive bone formation. Furthermore, our studies suggest the importance of modulating endogenous BMP-antagonist activity in therapeutic applications of BMP-induced osteogenesis.
-
conductive hearing loss in individuals with fibrodysplasia ossificans progressiva
American Journal of Audiology, 1999Co-Authors: Charles E Levy, Albert T Lash, Hal B Janoff, Frederick S KaplanAbstract:Fibrodysplasia ossificans progressiva (FOP) is a very rare Genetic Disorder that is characterized by progressive heterotopic ossification of soft tissues and congenital malformation of the great to...
Beatrice Latal - One of the best experts on this subject based on the ideXlab platform.
-
children with Genetic Disorders undergoing open heart surgery are they at increased risk for postoperative complications
Pediatric Critical Care Medicine, 2011Co-Authors: Carsten Doell, Vera Bernet, Luciano Molinari, Ingrid A Beck, Christian Balmer, Beatrice LatalAbstract:OBJECTIVES Children with congenital heart disease and Genetic Disorders may be at increased risk for postoperative mortality and morbidity compared with children with congenital heart disease alone. The aim of the present study was to determine differences in postcardiopulmonary bypass outcome between these two groups. DESIGN Prospective cohort study. SETTING Tertiary university children's hospital. PATIENTS We enrolled 211 infants (<1 yr) who underwent bypass surgery for congenital heart disease. Data on perioperative course were compared between infants with and without Genetic Disorders. Univariate analysis was followed by regression analysis to control for confounders. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We enrolled 148 infants without and 63 infants with a Genetic Disorder. The majority of infants with Genetic Disorders had trisomy 21 (n = 32), six had microdeletion 22q11, and 25 had other Genetic Disorders. There was no significant difference in mortality between infants with and without Genetic Disorders. An underlying Genetic Disorder was an independent risk factor for renal insufficiency (p = .003) and reintubation (p = .02). Trisomy 21 was an independent risk factor for chylothorax (p = .01) and sepsis (p = .05). The length of hospital stay was longer in infants with Genetic Disorders other than trisomy 21 compared with infants with trisomy 21 (p = .009). CONCLUSIONS Infants with congenital heart disease and Genetic Disorders are not at increased risk for postoperative mortality. However, a Genetic Disorder is a risk factor for reintubation and renal insufficiency, whereas infants with trisomy 21 have a higher risk of chylothorax and sepsis. Intensive care providers need to be aware of these differences in morbidity to improve management decisions and parental counseling.
G Frauscher - One of the best experts on this subject based on the ideXlab platform.
-
hereditary osteo onycho renal dysplasia with excess urinary pyridinoline cross links and abnormal kidney collagen cross linking
Nephron, 1995Co-Authors: B Lubec, K Arbeiter, W Ulrich, G FrauscherAbstract:HOOD syndrome is a rare Genetic Disorder also known as nail patella syndrome. Biochemical and molecular biological data are rare and not conclusive. Preliminary data suggest the involvement of collage
Aine Lawlor - One of the best experts on this subject based on the ideXlab platform.
-
hearing the lived experience of young women with a rare Genetic Disorder 22q11 2ds regarding integrated care
International Journal of Integrated Care, 2017Co-Authors: Lorna Kerin, Fiona Mcnicholas, Aine LawlorAbstract:Introduction : The lived experience of young people with chronic disease has seldom been heard in health research despite the clear policy imperative to hear the voices of children and young people as service users and rights holders. This participatory research sought to redress this by empowering young women with 22q11.2 Deletion Syndrome, a rare Genetic Disorder which can cause chronic, multiple and complex health difficulties, to express their lived experience of transitions from paediatric to adult care. Methods : Radically different from the old paradigm of positivist science, the transformative research methodology ‘Participatory Action Research’ (PAR) was chosen to empower participants by conducting research ‘with’ and not ‘on’ them, validating their lived experience and ability as service users to inform service provision and policy. Six young women with 22q11.2DS aged 21 to 35 years were recruited to a ‘Young Experts by Experience Panel’ (YEEP). Arts based, narrative methods including body map drawings, lifelines and photo-voice were employed to initially elicit qualitative themes. Subsequent focus group discussions explored these themes. Digital story methodology informed a short video highlighting the YEEP’s experience and recommendations regarding an integrated care clinic for children and young people with rare Genetic Disorders. Results : Research participation outcomes included enhanced health literacy, acceptance of diagnosis, peer support, self-advocacy, confidence, autonomy and a sense of belonging to a unique community. Emerging themes included acceptance of chronic illness, self-care management of mental health and wellbeing and the challenge of communicating with multiple care providers complicated by mild intellectual disability and speech and language difficulties. Identified health service needs included the need for an integrated care coordinator and an integrated multidisciplinary care clinic to support with the transition from paediatric to adult healthcare. Discussion : The young adult service users specified their preference for a ‘one stop shop’ to provide integrated care across their lifespan. They reported that the current absence of integrated care causes anxiety and fear as participants struggle to cope with explaining their rare Disorder to healthcare providers, to communicate effectively with clinicians from multiple disciplines and with their reluctant dependence on ageing parental carers to facilitate access to appropriate healthcare. Conclusions : Integrated care provision was identified by participants as the pathway to greater autonomy, self-care, successful transitions and positive health outcomes. Lessons learned : This participatory approach to research was an empowering process for young adult patients which resulted in a compelling request to policy makers to enable integrated care for rare chronic diseases. Additionally producing a visual digital story of the research process facilitated dissemination of young people’s voices to be heard in multiple settings, including clinical, academic, community and policy environments. Limitations : Notwithstanding the unique richness of the qualitative findings into the lived experience of young adult female service users, the research was not informed by the male young adult experience of their chronic Disorder due to lack of available male participants. Suggestions for future research : Further participatory research with children and young people with chronic rare diseases and their parents could usefully inform the development of an integrated care pathway as a model for chronic rare diseases. Such research should strive to include the perspective of both genders' perspective.
