Annual review of medicine
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The induction of hypometabolism in cells and organs to reduce ischemia damage holds enormous clinical promise in diverse fields, including treatment of stroke and heart attack. However, the thought that humans can undergo a severe hypometabolic state analogous to hibernation borders on science fiction. Some mammals can enter a severe hypothermic state during hibernation in which metabolic activity is extremely low, and yet full viability is restored when the animal arouses from such a state. ⋯ The beneficial effect of hypothermia, which reduces cellular metabolic demands, has many well-established clinical applications. However, severe hypothermia induced by clinical drugs is extremely difficult and is associated with dramatically increased rates of cardiac arrest for nonhibernators. The recent discovery of a biomolecule, 5'-AMP, which allows nonhibernating mammals to rapidly and safely enter severe hypothermia could remove this impediment and enable the wide adoption of hypothermia as a routine clinical tool.
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Annual review of medicine · Jan 2008
ReviewA decade of rituximab: improving survival outcomes in non-Hodgkin's lymphoma.
The anti-CD20 monoclonal antibody rituximab, first approved for clinical use in 1997, has changed the standard of care for many patients with non-Hodgkin's lymphoma (NHL). Recent data from large randomized clinical trials confirm that the addition of rituximab to standard chemotherapy regimens (chemoimmunotherapy) improves both response rates and survival outcomes in patients with follicular NHL and diffuse large B cell lymphoma (DLBCL), the two most common subtypes of NHL. Population-based analyses have found substantial improvements in NHL survival over the past decade; studies indicate that rituximab has favorably altered the long-term prognosis of follicular NHL and DLBCL patients. This review discusses the clinical development of rituximab-based therapies for patients with low-grade or follicular NHL and newly diagnosed DLBCL, highlighting recent key randomized trials with a focus on survival outcomes.
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Annual review of medicine · Jan 2007
ReviewUse of stents to treat intracranial cerebrovascular disease.
Intracranial atherosclerosis is a common cause of stroke. Although it has been recognized for decades, the lack of successful treatment strategies has limited clinical interest until recently. We review the natural history and pathophysiology of intracranial atherosclerosis. ⋯ Identification of appropriate candidates for treatment also remains a challenge, and our knowledge about the natural history of the disease is limited. At this time, patients with significant intracranial stenosis should receive information on the benefits and risks of revascularization therapy. Determining which patients should undergo revascularization procedures will require carefully planned, randomized clinical trials.
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Annual review of medicine · Jan 2007
ReviewDoes anti-IgE therapy help in asthma? Efficacy and controversies.
Omalizumab, a humanized monoclonal antibody against IgE, is clinically efficacious when it neutralizes almost all free IgE and reduces IgE receptors on basophils and mast cells. Asthmatic subjects on inhaled corticosteroids who are treated with omalizumab as an add-on therapy experience only modest benefits in symptoms and perhaps in quality of life, but the most significant effects are reductions in airway inflammation and in exacerbation rate. Airway obstruction and hyperresponsiveness do not change significantly. ⋯ The safety profile of omalizumab is very encouraging, although phase IV studies are ongoing to clarify the incidence of neoplasias. Because of its cost, omalizumab therapy may be most cost-effective in patients with severe and refractory asthma, particularly those with frequent exacerbations requiring hospital care. Further clinical studies are now evaluating the best place for omalizumab in the algorithm of asthma management.
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Annual review of medicine · Jan 2005
ReviewHematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system.
A vast literature exists on the biology of blood formation and regeneration under experimental and clinical conditions. The field of hematopoiesis was recently advanced by the capacity to purify to homogeneity primitive hematopoietic stem and progenitor cells. Isolation of cells at defined maturational stages has enhanced the understanding of the fundamental nature of stem cells, including how cell fate decisions are made, and this understanding is relevant to the development of other normal as well as malignant tissues. This review updates the basic biology of hematopoietic stem cells (HSC) and progenitors, the evolving use of purified HSC as grafts for clinical hematopoietic cell transplantation (HCT) including immune tolerance induction, and the application of HSC biology to other stem cell fields.