Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis

BACKGROUND: Nitric oxide (NO(•)) plays a pivotal role as a leishmanicidal agent in mouse macrophages. NO(• )resistant Escherichia coli and Mycobacterium tuberculosis have been associated with a severe outcome of these diseases. METHODS: In this study we evaluated the in vitro toxicity of nitric oxide for the promastigote stages of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis parasites, and the infectivity of the amastigote stage for human macrophages. Parasites were isolated from patients with cutaneous, mucosal or disseminated leishmaniasis, and NO(• )resistance was correlated with clinical presentation. RESULTS: Seventeen isolates of L. (L.) amazonensis or L. (V.) braziliensis promastigotes were killed by up to 8 mM of more of NaNO(2 )(pH 5.0) and therefore were defined as nitric oxide-susceptible. In contrast, eleven isolates that survived exposure to 16 mM NaNO(2 )were defined as nitric oxide-resistant. Patients infected with nitric oxide-resistant Leishmania had significantly larger lesions than patients infected with nitric oxide-susceptible isolates. Furthermore, nitric oxide-resistant L. (L.) amazonensis and L. (V.) braziliensis multiplied significantly better in human macrophages than nitric oxide-susceptible isolates. CONCLUSION: These data suggest that nitric oxide-resistance of Leishmania isolates confers a survival benefit for the parasites inside the macrophage, and possibly exacerbates the clinical course of human leishmaniasis

The association of psychiatric comorbidity and use of the emergency department among persons with substance use disorders: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>Psychiatric and substance use problems are commonly found to be contributing factors to frequent Emergency Department (ED) use, yet little research has focused on the association between substance use and psychiatric comorbidity. This study assesses the association of a psychiatric comorbidity on (ED) use among patients with substance use disorders (SUDs).</p> <p>Methods</p> <p>The study focuses on 6,865 patients who were diagnosed with SUDs in the ED of a large urban hospital in the southern United States from January 1994 – June 1998. Patients were grouped by type of substance use disorder. After examining frequency of visits by diagnosis, the sample was assigned to the following groups–alcohol dependence (ICD9 = 303), alcohol abuse (ICD9 = 305.0), cocaine dependence/abuse (ICD9 = 304.2, 305.6), and polysubstance/mixed use (ICD9 = 305.9). A patient was classified with psychiatric comorbidity if a psychiatric diagnosis appeared during any of the patient's visits. The following psychiatric diagnoses were included–schizophrenia/psychoses, bipolar disorder, depression, anxiety, and dementia (ICD-9 codes available upon request).</p> <p>Results</p> <p>Patients with SUDs and psychiatric comorbidity had significantly higher mean number of ER visits (mean = 5.2 SD = 8.7) than SUD patients without psychiatric comorbidity (mean = 2.5, SD = 3.7). In logistic regressions predicting several categorizations of heavier use of the ED (either 4+, 8+, 12+, 16+, or 20+ visits over the span of the study) SUD patients with psychiatric comorbidity had adjusted odds ratios of 3.0 to 5.6 (reference group = patients with SUDs but no psychiatric comorbidity). This association was found across all substance use diagnostic categories studied, with the strongest relationship observed among patients with cocaine disorders or alcohol dependence.</p> <p>Conclusion</p> <p>The results provide further support for the notion that the ED could and should serve as an important identification site for cost-effective intervention.</p

The Demography of Obesity

A steady rise in obesity prevalence over several decades has led to considerable scholarly interest in its causes and consequences. Demographers have contributed a great deal to this body of research by examining variations within and across populations, establishing its link to mortality and morbidity, providing forecast and projections of future levels, and considering how its’ presence is variable by demographic characteristics. This chapter begins with a review of overall global trends in obesity and a discussion of the evolution of research on this topic – including background on the measures used to track obesity prevalence. Next, it offers a summary of how obesity varies by key demographic variables, followed by a discussion of its health and social consequences. Population shifts that contribute to increased obesity prevalence are considered next. The chapter concludes with methodological approaches and challenges, as well as future research directions

Der Körper als Zeichen!?

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