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Rachmilewitz E.A.,Wolfson Medical Center | Giardina P.J.,New York Presbyterian Hospital
Blood | Year: 2011

The purpose of this article is to set forth our approach to diagnosing and managing the thalassemias, including β-thalassemia intermedia and β-thalassemia major. The article begins by briefly describing recent advances in our understanding of the pathophysiology of thalassemia. In the discussion on diagnosing the condition, we cover the development of improved diagnostic tools, including the use of very small fetal DNA samples to detectsingle point mutations with great reliability for prenatal diagnosis of homozygous thalassemia. In our description of treatment strategies, we focus on how we deal with clinical manifestations and long-term complications using the most effective current treatment methods for β-thalassemia. The discussion of disease management focuses on our use of transfusion therapy and the newly developed oral iron chelators, deferiprone and deferasirox.We also deal with splenectomy and how we manage endocrinopathies and cardiac complications. In addition, we describe our use of hematopoietic stem cell transplantation, which has produced cure rates as high as 97%, and the use of cord blood transplantation. Finally, we briefly touch on therapies that might be effective in the near future, including new fetal hemoglobin inducers and gene therapy. © 2011 by The American Society of Hematology.


Katz U.,Immunology and Allergy Unit | Katz U.,Tel Aviv University | Zandman-Goddard G.,Tel Aviv University | Zandman-Goddard G.,Wolfson Medical Center
Autoimmunity Reviews | Year: 2010

Purpose: To review and update drug-induced lupus (DIL) with emphasis on the characteristics of anti-TNF-induced lupus. Results: DIL is an autoimmune phenomenon triggered by a given drug and resulting in a syndrome sharing several features of systemic lupus erythematosus (SLE). Drugs like procainamide and hydralazine have been strongly associated with the development of DIL. During the past years several cases of DIL related to biologic therapy with anti-TNF drugs were reported. From the analysis of the unusual characteristics of these cases some conclusions may be drawn: anti-TNF-induced DIL may present with classical SLE dermatologic symptoms, hypocomplementemia, an increased frequency of significant anti-dsDNA antibody titers and a decreased incidence of anti-histone antibodies, all these atypical findings in classical DIL. Conclusions: Anti-TNF-induced DIL may be a unique form of the disease or may possibly result from the unmasking of latent idiopathic SLE. © 2010 Elsevier B.V.


Rosario C.,Tel Aviv University | Zandman-Goddard G.,Tel Aviv University | Zandman-Goddard G.,Wolfson Medical Center | Meyron-Holtz E.G.,Technion - Israel Institute of Technology | And 2 more authors.
BMC Medicine | Year: 2013

Background: Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients.Discussion: There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still's disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm.Summary: Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed " Hyperferritinemic Syndrome". © 2013 Rosário et al.; licensee BioMed Central Ltd.


Musallam K.M.,University of Milan | Rivella S.,Cornell University | Vichinsky E.,Childrens Hospital Oakland Research Institute | Rachmilewitz E.A.,Wolfson Medical Center
Haematologica | Year: 2013

Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration. © 2013 Ferrata Storti Foundation.


Dabby R.,Wolfson Medical Center | Dabby R.,Tel Aviv University
Current Neurology and Neuroscience Reports | Year: 2012

Voltage-gated sodium channels play a pivotal role in pain transmission. They are widely expressed in nociceptive neurons, and participate in the generation of action potentials. Alteration in ionic conduction of these channels causes abnormal electrical firing, thus renders neurons hyperexcitable. So far, mutations in the Na v1.7 sodium channel, which is expressed in the dorsal root ganglia cells and sympathetic neurons, have been described to cause perturbations in pain sensation. Until recently, gain-of-function Na v1.7 mutations were known to cause two neuropathic pain syndromes: inherited erythromelalgia and paroxysmal extreme pain syndrome. These syndromes are inherited in a dominant trait; they usually begin in childhood or infancy, and are characterized by attacks of severe neuropathic pain accompanied with autonomic symptoms. Recently, small fiber neuropathy and chronic nonparoxysmal pain have been described in patients harboring gain-of-function mutations in Na v1.7 channel. Loss-of-function mutations in Na v1.7 are extremely rare, and invariably cause congenital inability to perceive pain. © 2011 Springer Science+Business Media, LLC.

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