The Mount Sinai journal of medicine, New York
-
Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. ⋯ The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease-related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research.
-
The transition from either epidemiological observation or the bench to rigorously tested clinical trials in patients with Alzheimer's disease is crucial in understanding which treatments are beneficial to patients. The amyloid hypothesis has undergone scrutiny recently, as many trials aimed at reducing amyloid and plaque have been completed or are in the testing phase. ⋯ Other therapies targeting hyperphosphorylated tau and novel targets such as enhancement of mitochondrial function, serotonin receptors, receptor for advanced glycation end products, and nerve growth factor, as well as other strategies, are discussed. A brief review of the current Food and Drug Administration-approved treatments is included.
-
The autophagy pathway is the major degradation pathway of the cell for long-lived proteins and organelles. Dysfunction of autophagy has been linked to several neurodegenerative disorders that are associated with an accumulation of misfolded protein aggregates. Alzheimer's disease, the most common neurodegenerative disorder, is characterized by 2 aggregate forms, tau tangles and amyloid-beta plaques. ⋯ However, the precise role of autophagy in Alzheimer's disease pathogenesis is still under contention. One hypothesis is that aberrant autophagy induction results in an accumulation of autophagic vacuoles containing amyloid-beta and the components necessary for its generation, whereas other evidence points to impaired autophagic clearance or even an overall reduction in autophagic activity playing a role in Alzheimer's disease pathogenesis. In this review, we discuss the current evidence linking autophagy to Alzheimer's disease as well as the uncertainty over the exact role and level of autophagic regulation in the pathogenic mechanism of Alzheimer's disease.
-
Preventable maternal and neonatal mortalities still occur, despite the wonders of today's technologically advanced healthcare system. Delivering high-quality, consistent care is the goal of every provider. ⋯ Obstetrics departments should be striving for a climate of patient safety, one that includes a just, reporting, and learning culture. This article discusses the various components of a safety culture as well as some of the advances that are being made in the field to improve the quality of care in obstetrics.
-
The majority of newly emerging diseases are zoonoses caused by pathogens transmitted directly or indirectly through arthropod vectors to humans. Transmission chains leading to human infection frequently involve intermediate vertebrate hosts, including wildlife and domestic animals. Animal-based surveillance of domestic and wild animals for zoonotic pathogens is a global challenge. ⋯ Novel schemes for preventing spillover of human pathogens from animal reservoir hosts can spring only from an understanding of the ecological context and biological interactions that result in zoonotic disease emergence. Although the benefits derived from investments to improve surveillance and knowledge of zoonotic pathogens circulating among wildlife reservoir populations are uncertain, our experience with human immunodeficiency virus and the pandemic influenza inform us of the outcomes that we can expect by relying on detection of post-spillover events among sentinel humans. Mt Sinai J Med 76:421-428, 2009. (c) 2009 Mount Sinai School of Medicine.