Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Sep 2010
HIV/AIDS: vaccines and alternate strategies for treatment and prevention.
The symposium "HIV/AIDS: Vaccines and Alternate Strategies for Treatment and Prevention" brought together HIV vaccine researchers to discuss the latest developments in the field. From basic discoveries in virus diversity and mechanisms of neutralization by antibodies to nonhuman primate research and clinical trials of vaccine candidates in volunteers, scientists are making great strides in understanding the mechanisms that may protect against HIV and pathways to achieve this protection through vaccination.
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Ann. N. Y. Acad. Sci. · Sep 2010
ReviewIs it possible to reduce obstetrical brachial plexus palsy by optimal management of shoulder dystocia?
Obstetrical brachial plexus palsies (OBPP) have been historically attributed to the impaction of the fetal shoulder behind the symphysis pubis and to excessive lateral traction of the fetal head during maneuvers to deliver the fetal shoulders in shoulder dystocia. Shoulder dystocia is indeed a major risk factor as it increases the risk for OBPP 100-fold. The incidence of OBPP following shoulder dystocia varies widely from 4% to 40%. ⋯ The propulsive forces of labor, intrauterine maladaptation, and compression of the posterior shoulder against the sacral promontory as well as uterine anomalies are possible intrauterine causes of OBPP. Many risk factors for OBPP may be unpredictable. Early identification of risk factors for shoulder dystocia, as well as appropriate management when it occurs, may improve our ability to prevent the occurrence of OBPP in those cases that are caused by shoulder dystocia.
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Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with beta-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. ⋯ These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in beta-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in beta-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries.
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Ann. N. Y. Acad. Sci. · Aug 2010
ReviewThe challenge of obtaining therapeutic levels of genetically modified hematopoietic stem cells in beta-thalassemia patients.
Hematopoietic stem cells (HSCs) function to provide the individual with a continuing supply of blood cells over many decades. To this end, HSCs have evolved unique mechanisms for self-preservation, including resistance to viral infection. Unfortunately, this characteristic may impede the ability to achieve high levels of gene transfer mediated by HIV-based lentiviral vectors. ⋯ In particular, the study of beta-thalassemia patients that underwent allogeneic stem cell transplantation and developed stable, long-term mixed chimerism suggests that HSC gene transfer levels of greater than 25% will be needed for a robust therapeutic effect in such patients. Available pre-clinical and clinical trial lentiviral gene transfer studies suggest that improvements are needed to achieve this goal. Here, we review what level of gene transfer is needed in the context of varying degrees of beta-globin deficiency, what level is currently achievable, and the areas of research which may be fruitful in improving the likelihood of success for patients with the severest forms of beta-thalassemia.
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Ann. N. Y. Acad. Sci. · Aug 2010
Detection of the cardiovascular complications of thalassemia by echocardiography.
The thalassemia syndromes are associated with cardiovascular complications, which differ with the varying phenotypes encountered. The well-recognized paradigm of heart failure induced by myocardial iron overload, in thalassemia major (TM), has now been joined by pulmonary arterial hypertension (mostly seen in thalassemia intermedia) among other more subtle disorders of the cardiovascular system, including endothelial dysfunction. ⋯ Echocardiography remains an indispensable tool in the cardiovascular assessment of patients, it provides many insights into cardiovascular function, and its use allows improved management of patients. It is particularly suited to assess diastolic function, diagnose intracardiac masses (usually thrombus), and assess right ventricular function and pulmonary pressure.