Annals of the New York Academy of Sciences
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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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In the United States, cancer is the second most common cause of death and it is expected that about 562,340 Americans will have died of cancer in 2009. Bone cancer pain is common in patients with advanced breast, prostate, and lung cancer as these tumors have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone, they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, fractures, pain, and anemia. ⋯ However, several recently introduced models of bone cancer pain, which closely mirror the human condition, are providing insight into the mechanisms that drive bone cancer pain and guide the development of mechanism-based therapies to treat the cancer pain. Several of these mechanism-based therapies have now entered human clinical trials. If successful, these therapies have the potential to significantly enlarge the repertoire of modalities that can be used to treat bone cancer pain and improve the quality of life, functional status, and survival of patients with bone cancer.
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The pathophysiology of fibromyalgia (FM) is not completely understood. The disease is characterized by a central sensitization with an amplification of pain perception. A combination of interactions among external stressors, behavioral constructs, neurotransmitters, hormones, immune, and sympathetic nervous systems appears to be involved. ⋯ Recent data highlight the putative role of cytokines in the pathogenesis of FM. The autonomic nervous system is implicated in the maintenance of the physiological homeostasis and sympathetic activity appears increased in FM. Neuropeptide Y and its receptors Y1 and Y2 seem to have a complex role in pain modulation.