Elevated Blood Lead Concentrations and Vitamin D Deficiency in Winter and Summer in Young Urban Children

BACKGROUND: It is widely recognized that blood lead concentrations are higher in the summer than in winter. Although the effects of some environmental factors such as lead in dust on this phenomenon have been studied, relationships to sunlight-induced vitamin D synthesis have not been adequately investigated. Vitamin D status is influenced by the diet, sunlight exposure, age, skin pigmentation, and other factors, and may modify gastrointestinal lead absorption or release of lead stored in bones into the bloodstream. OBJECTIVE AND METHODS: We collected paired blood samples from 142 young, urban African-American and Hispanic children in the winter and summer to study the seasonal increase in blood lead and its relationships to vitamin D nutrition, age, and race. RESULTS: A winter/summer (W/S) increase in blood lead concentrations of 32.4% was found for children 1–3 years of age. There was a smaller W/S increase of 13.0% in children 4–8 years of age. None of the 51 Hispanic children had an elevated blood lead concentration (≥ 10 μg/dL) during the winter, and only one had an elevated summertime concentration. In contrast, elevated blood lead concentrations were frequent in the 91 African-American children, especially those 1–3 years of age. For the latter, the percentage with elevated blood lead levels increased from 12.2% in winter to 22.5% in summer. A 1.2% W/S increase in serum 25-hydroxy-vitamin D (serum 25-OH-D) concentrations was found for children 1–3 years of age. However, in children 4–8 years of age the W/S increase in serum 25-OH-D was much larger—33.6%. The percentages of children with low (< 16 μg/L) serum 25-OH-D concentrations were 12.0% in winter and 0.7% in summer and were consistently greater in African-American than in Hispanic children. The seasonal increases in blood lead and serum 25-OH-D in children 4–8 years of age were significantly associated. CONCLUSION: The higher summertime serum 25-OH-D concentrations for the 4- to 8-year-old children are likely caused by increased sunlight-induced vitamin D synthesis and may contribute to the seasonal increase in blood lead. Age and race are key factors that affect blood lead and vitamin D nutrition, as well as their interactions, in young urban children

Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF: effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion

BACKGROUND: Nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) all play important roles in the development of the peripheral sensory nervous system. Additionally, these growth factors are proposed to modulate the properties of the sensory system in the adult under pathological conditions brought about by nerve injury or inflammation. We have examined the effects of NGF, GDNF and BDNF on adult rat trigeminal ganglion (TG) neurons in culture to gain a better understanding of how these growth factors alter the cytochemical and functional phenotype of these neurons, with special attention to properties associated with nociception. RESULTS: Compared with no growth factor controls, GDNF, at 1 and 100 ng/ml, significantly increased by nearly 100% the number of neurons in culture at 5 days post-plating. A significant, positive, linear trend of increasing neuron number as a function of BDNF concentration was observed, also peaking at nearly 100%. NGF treatment was without effect. Chronic treatment with NGF and GDNF significantly and concentration-dependently increased 100 nM capsaicin (CAP)-evoked calcitonin gene-related peptide (CGRP) release, reaching approximately 300% at the highest concentration tested (100 ng/ml). Also, NGF and GDNF each augmented anandamide (AEA)- and arachidonyl-2-chloroethylamide (ACEA)-evoked CGRP release, while BDNF was without effect. Utilizing immunohistochemistry to account for the proportions of TRPV1- or CGRP-positive neurons under each growth factor treatment condition and then standardizing evoked CGRP release to these proportions, we observed that NGF was much more effective in enhancing CAP- and 50 mM K(+)-evoked CGRP release than was GDNF. Furthermore, NGF and GDNF each altered the concentration-response function for CAP- and AEA-evoked CGRP release, increasing the E(max )without altering the EC(50 )for either compound. CONCLUSIONS: Taken together, our results illustrate that NGF, GDNF and BDNF differentially alter TG sensory neuron survival, neurochemical properties and TRPV1-mediated neuropeptide release in culture. In particular, our findings suggest that GDNF and NGF differentially modulate TRPV1-mediated neuropeptide secretion sensitivity, with NGF having a much greater effect on a per neuron basis than GDNF. These findings are discussed in relation to possible therapeutic roles for growth factors or their modulators in pathological pain states, especially as these relate to the trigeminal system

Influenza Pandemics of the 20th Century

Influenza A virus infection created confusion in distinguishing true pandemics, pseudopandemics, and epidemics

Lifespan extension and the doctrine of double effect

Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning

The Role of Neutrophils during Mild and Severe Influenza Virus Infections of Mice

Neutrophils have been implicated in both protective and pathological responses following influenza virus infections. We have used mAb 1A8 (anti-Ly6G) to specifically deplete LyG6high neutrophils and induce neutropenia in mice infected with virus strains known to differ in virulence. Mice were also treated with mAb RB6-8C5 (anti-Ly6C/G or anti-Gr-1), a mAb widely used to investigate the role of neutrophils in mice that has been shown to bind and deplete additional leukocyte subsets. Using mAb 1A8, we confirm the beneficial role of neutrophils in mice infected with virus strains of intermediate (HKx31; H3N2) or high (PR8; H1N1) virulence whereas treatment of mice infected with an avirulent strain (BJx109; H3N2) did not affect disease or virus replication. Treatment of BJx109-infected mice with mAb RB6-8C5 was, however, associated with significant weight loss and enhanced virus replication indicating that other Gr-1+ cells, not neutrophils, limit disease severity during mild influenza infections

Appropriateness of antibiotic treatment in intravenous drug users, a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Infectious disease is often the reason for intravenous drug users being seen in a clinical setting. The objective of this study was to evaluate the appropriateness of treatment and outcomes for this patient population in a hospital setting.</p> <p>Methods</p> <p>Retrospective study of all intravenous drug users hospitalized for treatment of infectious diseases and seen by infectious diseases specialists 1/2001–12/2006 at a university hospital. Treatment was administered according to guidelines when possible or to alternative treatment program in case of patients for whom adherence to standard protocols was not possible. Outcomes were defined with respect to appropriateness of treatment, hospital readmission, relapse and mortality rates. For statistical analysis adjustment for multiple hospitalizations of individual patients was made by using a generalized estimating equation.</p> <p>Results</p> <p>The total number of hospitalizations for infectious diseases was 344 among 216 intravenous drug users. Skin and soft tissue infections (n = 129, 37.5% of hospitalizations), pneumonia (n = 75, 21.8%) and endocarditis (n = 54, 15.7%) were most prevalent. Multiple infections were present in 25%. Treatment was according to standard guidelines for 78.5%, according to an alternative recommended program for 11.3%, and not according to guidelines or by the infectious diseases specialist advice for 10.2% of hospitalizations. Psychiatric disorders had a significant negative impact on compliance (compliance problems in 19.8% of hospitalizations) in multiple logistic regression analysis (OR = 2.4, CI 1.1–5.1, p = 0.03). The overall readmission rate and relapse rate within 30 days was 13.7% and 3.8%, respectively. Both non-compliant patient behavior (OR = 3.7, CI 1.3–10.8, p = 0.02) and non-adherence to treatment guidelines (OR = 3.3, CI 1.1–9.7, p = 0.03) were associated with a significant increase in the relapse rate in univariate analysis. In 590 person-years of follow-up, 24.6% of the patients died: 6.4% died during hospitalization (1.2% infection-related) and 13.6% of patients died after discharge.</p> <p>Conclusion</p> <p>Appropriate antibiotic therapy according to standard guidelines in hospitalized intravenous drug users is generally practicable and successful. In a minority alternative treatments may be indicated, although associated with a higher risk of relapse.</p