Mount Sinai Journal of Medicine最新文献

There is an important correlation between vascular risk factors and nonspecific imaging findings in the brain such as white-matter hyperintensities. These vascular risk factors are also associated with dementia and lesser forms of cognitive impairment. One hypothesis is that these vascular risk factors lead to disruption of connective networks in the central nervous system that are supported by myelinated white-matter fibers, which in turn lead to deficits in functional signaling between various brain regions. Another possibility is an alteration of the neurovascular coupling due to vascular risk factors. This reduced functional signaling contributes to the cognitive deficits in persons harboring these vascular risk factors. Lifestyle changes may restore some of these functional deficits through brain plasticity. It is imperative that preclinical diagnostic techniques are developed to identify these early brain changes in persons harboring vascular risk factors, as such efforts may improve primary and secondary prevention efforts. Recently developed imaging techniques may provide objective imaging biomarkers to measure the structural and functional brain changes in persons with vascular risk factors and resulting subclinical atherosclerotic disease. This article reviews a few of these novel imaging techniques.

Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This article reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis.

Cardiovascular disease is the leading cause of death worldwide, affecting not only high-income but also low- and middle-income countries. Nearly 80 percent of all estimated cardiovascular disease-related deaths worldwide now occur in low- and middle-income countries, where nearly 30 percent of all deaths are attributable to cardiovascular disease. The health burden of cardiovascular disease and other chronic diseases is also accompanied by a significant deleterious economic impact at the level of both national economies and households. The global trends in the health and economic burden of cardiovascular disease provide a compelling argument in support of prioritizing urgent yet carefully planned efforts to prevent and control cardiovascular disease worldwide-and especially in low- and middle-income countries. After decades of escalating efforts to draw attention to the high burden of cardiovascular disease and other chronic diseases, this critically important issue is now emerging as a more central part of the global health and development agenda. The breadth of behavioral, biological, social, environmental, and systems-level factors that contribute to cardiovascular disease necessitates multisectoral approaches across the lifecourse that promote healthful lifestyles, reduce risk, and reduce cardiovascular-disease morbidity and mortality through the delivery of quality health care services. Given that the complex interactions among the determinants of cardiovascular disease vary in different contexts, real progress in control efforts will come through approaches that are driven by a country's disease burden and risk profile, capacities, resources, and priorities-approaches that are led by a country's key decision-makers and stakeholders, including governments, civil society, the private sector, and communities. Many countries are already establishing efforts to address chronic diseases. In addition to these locally driven efforts, success will require active engagement and sustained action from a wide array of stakeholders operating at global and regional levels.

The involvement of vascular factors in Alzheimer dementia was first appreciated over 100 years ago. Recently, significant advances in our understanding of these brain-vascular relationships have taken place. Vascular cognitive impairment is now recognized as a distinct group of interrelated vascular-based neurological insults that can accumulate and lead to dementia. Importantly, the pathology of vascular cognitive impairment extends far beyond brain destruction wrought by major stroke. Other subtle changes may also arise that contribute to vascular cognitive impairment and dementia, including subclinical stroke, white-matter changes such as hyperintensities and lipohyalinosis, small lacunar infarcts, cerebral hypoperfusion, and compromise of the blood-brain barrier. In this review we critically examine the emerging body of evidence that relates atherosclerotic risk factors, brain functioning, and Alzheimer disease.

Cardiovascular-disease prevention is often inadequate due to several factors. Lack of professional adherence to guidelines, unaffordable medication, and lack of patients' adherence to treatment are the most important. It has been suggested that an affordable, fixed-dose combination drug containing evidence-based active compounds could improve cardiovascular prevention by improving patients' adherence to treatment. The available evidence suggests that the polypill strategy can achieve this objective and it will gain a place in the therapeutic armamentarium for the prevention of cardiovascular events in patients at high risk.

Background: AA amyloidosis is a systemic disease characterized by the extracellular deposition of amyloid fibrils derived from the acute-phase reactant serum amyloid A protein. It is typically a consequence of chronic inflammatory conditions like rheumatoid arthritis or Crohn's disease, although more patients are being identified who have more unusual causes or no known inflammatory stimulus.

Methods: We performed a retrospective chart review of all patients with AA amyloidosis seen at Mount Sinai during the period of 1997-2012. Particular attention was paid to the patients' underlying diseases, extent of organ involvement, levels of inflammatory markers and proinflammatory cytokines, presence of pyrin gene mutations, and outcomes.

Results: Forty-three patients were seen at Mount Sinai with AA amyloidosis during this period. The most common underlying diseases were rheumatoid arthritis (21%) and Crohn's disease (16%), though 21% of patients were considered to have idiopathic AA amyloid after an extensive search found no underlying inflammatory disease. Almost all patients (95%) had renal involvement based on biopsy or clinical criteria, with 19 patients (44%) eventually requiring dialysis and 5 (12%) undergoing renal transplantation. Inflammatory markers were elevated in most patients; however, interleukin-6 was the only consistently elevated cytokine. Three patients (of 9 tested) were found to be positive for the E148Q pyrin gene mutation.

Conclusions: Our study confirms the increasing number of patients being seen with idiopathic AA amyloidosis. More research is needed to determine if these patients have an underlying genetic susceptibility encoded in pyrin or other genes. Our study also confirms the dominance of renal disease in this population. The elevated levels of interleukin-6, in comparison with other cytokines, could represent a therapeutic target.

Traditional risk factors explain most of the risk associated with coronary heart disease, and after adjustment for risk factors family history was believed to contribute very little to population-attributable risk of coronary heart disease. However, the INTERHEART study demonstrated an independent association of family history of coronary heart disease with acute myocardial infarction. To assess this relationship more comprehensively in multiple datasets in different populations, we carried out a detailed review of the available evidence. Case-control studies involving 17,202 cases and 30,088 controls yielded a pooled unadjusted odds ratio (random-effects model, overall I(2) = 64.6%, P = 0.000) of 2.03 (95% confidence interval: 1.79-2.30), whereas cohort studies that included 313,837 individuals yielded an unadjusted relative risk for future coronary heart disease (random-effects model, overall I(2) = 88.7%, P = 0.000) of 1.60 (95% confidence interval: 1.44-1.77). Although the presence of family history of coronary heart disease indicates a cumulative exposure of shared genes and environment, the risk estimates for family history did not attenuate significantly after adjustment for conventional coronary heart disease risk factors in several studies. It is probably an oversimplification to dichotomize the family history variable into a simple "yes" or "no" risk factor, as the significance of family history is influenced by several variables, such as age, sex, number of relatives, and age at onset of disease in the relatives. Moreover, a quantitative risk-assessment model for the family history variable, such as the "family risk score," has a positive linear relationship with coronary heart disease. More studies are warranted to assess the benefits and risks of intensive interventions, both targeted individually and at the family level, among individuals with a valid family history and borderline elevated risk factors.

Atherosclerotic vascular disease not only remains the leading cause of death in the Western countries, but it has become the most common cause of morbidity and mortality in the low- and middle-income countries as well. Therefore, better understanding of the pathogenesis of atherosclerotic disease and its prevention are of fundamental importance. It is well known that it affects sequentially the aorta followed by coronary, carotid, peripheral, and intracerebral arteries, with some individual variability. The mechanisms of progression are similar in each of the beds, with increasing lipid accumulation in the arterial wall along with macrophages and T-cell infiltration, paucity of smooth-muscle cell proliferation and collagen deposition, and endothelial-cell dysfunction and hypercoagulability playing an important role at the time of acute manifestations of the disease. Fundamental to this inflammatory process is the presence of classic risk factors, regardless of the involved territory. Therefore, the concept of palliative treatment must be reserved for only those who have progressed beyond preventive measures.