Prospective study of particulate air pollution exposures, subclinical atherosclerosis, and clinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45-84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD.

Differences among heat-treated, raw, and commercial peanut extracts by skin testing and immunoblotting.

BACKGROUND: Peanut allergenicity has been reported to be influenced by heat treatment, yet the commonly available extracts for skin prick testing (SPT) are derived from raw extracts. OBJECTIVE: To assess the effect of heat treatment on the SPT reactivity and specific IgE binding to peanut. METHODS: Three commercial extracts and 3 laboratory-prepared extracts, including raw, roasted, and boiled, were used for SPT in 19 patients with suspected peanut allergy and in 4 individuals who eat peanut without any symptoms. Serum samples were obtained to measure total IgE in addition to specific IgE binding to the study extracts by immunoblotting. Peanut allergy was confirmed with challenge test unless the individual had a convincing history of a severe reaction. RESULTS: Eleven study participants were considered peanut allergic based on a strong history or positive challenge test result. SPT with the prepared and commercial reagents showed that the boiled extract had the highest specificity (67% vs 42%-63% for the other extracts). The prepared extracts showed similar SPT sensitivity (81%). Three patients with a history of severe reaction and elevated specific IgE levels to peanut to the 3 study extracts had variable SPT reactivity to 1 or more of the commercial extracts. IgE binding to Ara h 2 was found in nearly all patients, regardless of their clinical reactivity. CONCLUSIONS: None of the extracts tested showed optimal diagnostic reliability regarding both sensitivity and specificity. Perhaps testing should be performed with multiple individual extracts prepared by different methods.

Underexpression and overexpression of Fas and Fas ligand: a double-edged sword.

OBJECTIVE: To compare autoimmune lymphoproliferative syndrome (ALPS) and Stevens-Johnson syndrome (SJS) with respect to the defects in Fas- and Fas ligand (FasL)-mediated apoptosis. DATA SOURCES: Selected reviews, case reports, and original studies were searched in PubMed and MEDLINE for the keywords ALPS, SJS, Fas, FasL, and apoptosis. STUDY SELECTION: Case reports of ALPS and SJS were selected as examples of Fas- and FasL-mediated diseases. In addition, we selected articles that examined the pathophysiology of apoptosis in the context of Fas-FasL interaction. RESULTS: Failure to initiate apoptosis of abnormal T lymphocytes occurs in such diseases as ALPS, leading to the accumulation of double negative T cells with an increase in autoimmunity. In contrast to apoptotic failure, SJS is associated with a pathological increase in programmed keratinocyte cell death. CONCLUSION: The consequences of dysregulated Fas- and FasL-mediated apoptosis leads to self-reactivity, malignant transformation, and immune dysfunction. An understanding of underlying mechanisms and qualitative assessment of Fas and FasL may have clinical benefits when control of these homeostatic mechanisms is in question.

C1-esterase inhibitor autoantibodies in a patient with acute tongue swelling.

Angioedema occurs when there is fluid leakage into the deep dermis of the skin and underlying subcutaneous tissues. Affected individuals usually present with swelling of the face or extremities. Acquired angioedema is an uncommon but potentially life-threatening disease in the older adult population. After the individual is cleared of the initial danger period, a thorough workup for an underlying etiology must be done. We report a 62-year-old male presenting with significant tongue swelling who was diagnosed with acquired angioedema. He had autoantibodies to C1 esterase inhibitor and was subsequently diagnosed with a lymphoma. Angioedema should be recognized by clinicians as a potential presentation of a more ominous malignancy.

Adverse drug reactions: types and treatment options.

Drug hypersensitivity results from interactions between a pharmacologic agent and the human immune system. These types of reactions constitute only a small subset of all adverse drug reactions. Allergic reactions to medications represent a specific class of drug hypersensitivity reactions mediated by IgE. Immune-mediated drug reactions may be discussed generally in the Gell and Coombs classification system, a widely accepted conceptual framework for understanding complex immune reactions. However, some reactions involve additional, poorly understood mechanisms that are not easily classified. Identifiable risk factors for drug hypersensitivity reactions include age, female gender, concurrent illnesses, and previous hypersensitivity to related drugs. Drug hypersensitivity is a clinical diagnosis based on available data. Laboratory testing may be useful, with skin testing providing the greatest specificity. Treatment is largely supportive and includes discontinuation of the offending medication, symptomatic treatment, and patient education. Patients with penicillin allergy should avoid carbapenems, and caution should be used in prescribing cephalosporins in these patients. Reactions to radiocontrast media can be limited by pretreatment with prednisone, diphenhydramine, and either ephedrine or a histamine H2-receptor antagonist.

A current review of Ebola virus: pathogenesis, clinical presentation, and diagnostic assessment.

Ebola hemorrhagic fever (EHF) is an acute viral syndrome that presents with fever and an ensuing bleeding diathesis that is marked by high mortality in human and nonhuman primates. Fatality rates are between 50% and 100%. Due to its lethal nature, this filovirus is classified as a biological class 4 pathogen. The natural reservoir of the virus is unknown. As a result, little is understood about how Ebola virus is transmitted or how it replicates in its host. Although the primary source of infection is unknown, the epidemiologic mode of transmission is well defined. A variety of tests have proven to be specific and useful for Ebola virus identification. There is no FDA-approved antiviral treatment for EHF. Incubation ranges from 2 to 21 days. Patients who are able to mount an immune response to the virus will begin to recover in 7 to 10 days and start a period of prolonged convalescence. Supportive management of infected patients is the primary method of treatment, with particular attention to maintenance of hydration, circulatory volume, blood pressure, and the provision of supplemental oxygen. Since there is no specific treatment outside of supportive management and palliative care, containment of this potentially lethal virus is paramount. In almost all outbreaks of EHF, the fatality rate among health care workers with documented infections was higher than that of non-health care workers.

Ebola virus: immune mechanisms of protection and vaccine development.

Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapon-grade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine.

Exploring Alternative Models of Complex Patient Management with Artificial Neural Networks.

This study applied an unsupervised neural network modeling process to test data of the National Board of Medical Examiners (NBME) Computer-based Clinical Scenarios (CCS) to identify new performance categories and validate this process as a scoring technique. The classifications resulting from this neural network modeling were consistent with the NBME model in that highly rated NMBE performances (ratings of 7 or 8) were clustered together on the neural network output grid. Very low performance ratings appeared to share few common features and were accordingly classified at isolated nodes. This clustering was reproducible across three separately trained networks with greater than 80% agreement in two of the three networks trained. However, the neural network also contained performance clusters where disparate NBME-based ratings ranged from 1 (worst) to 8 (best). Here, agreement between networks was less than 60%. Through visualization of the search strategies (search path mapping), this neural network clustering was found to be sensitive to quantitative and qualitative test selections such as excessive usage of irrelevant tests reflecting broader behavioral classification in some instances. A disparity between NBME ratings and an independent human rating system was detected by the neural network model since disagreement among raters was also reflected by a lack of neural network performance clustering. Agreement between rating systems, however, was correlated with neural network clustering for 92% of the highly rated performances.