Schwartz Formula: Is One k-Coefficient Adequate for All Children?

Background/Objective

Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population.

Patients/Methods

We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort.

Results

In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient.

Conclusions

The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance.     

Changes in plant chemical defenses and nutritional quality as a function of ontogeny in <Emphasis Type="Italic">Plantago lanceolata</Emphasis> (Plantaginaceae)

Numerous empirical studies have examined ontogenetic trajectories in plant defenses but only a few have explored the potential mechanisms underlying those patterns. Furthermore, most documented ontogenetic trajectories in plant defenses have generally concentrated on aboveground tissues; thus, our knowledge regarding whole plant trends in plant defenses throughout development or potential allocation constraints between growth and defenses is limited. Here, we document changes in plant biomass, nutritional quality and chemical defenses for below- and aboveground tissues across seven age classes of Plantago lanceolata (Plantaginaceae) to evaluate: (1) partial and whole plant ontogenetic trajectories in constitutive chemical defenses and nutritional quality, and (2) the role of resource allocation constraints, namely root:shoot (R:S) ratios, in explaining whole plant investment in chemical defenses over time. Overall investment in iridoid glycosides (IGs) significantly increased, while water and nitrogen concentrations in shoot tissues decreased with plant age. Significant variation in IG content between shoot and root tissues across development was observed: allocation of IGs into root tissues linearly increased from younger to older plants, while non-linear shifts in allocation of IGs during ontogeny were observed for shoot tissues. Finally, R:S ratios only weakly explained overall allocation of resources into defenses, with young stages showing a positive relationship, while older stages showed a negative relationship between R:S ratios and IG concentrations. Ontogenetic trajectories in plant quality and defenses within and among plant tissues can strongly influence insect herbivores’ performance and/or predation risk; thus, they are likely to play a significant role in mediating species interactions.     

Strongyloidiasis and Infective Dermatitis Alter Human T Lymphotropic Virus-1 Clonality in vivo

Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH), appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone). A newly developed biodiversity estimator called “DivE” was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance) of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1⁺ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1⁺ clones.     

Secretory structures at syconia and flowers of Ficus enormis (Moraceae): A specialization at ostiolar bracts and the first report of inflorescence colleters

The fig (Ficus L.) infructescence, called syconium, is a receptacle with an apical opening, the ostiole, closed by bracts. The ostiolar bracts produce an exudate, which is rather conspicuous in some species. It has not been histochemically analyzed yet, and the structures responsible for its production are still unknown. Some wild growing species of Ficus from Brazil produce high amounts of this ostiolar exudate. Ficus enormis (Mart. ex Miq.) Miq. grows as trees or shrubs in the Atlantic rainforest. Our goal was to identify the secretory structures present in the inflorescence and, to characterize histochemically the ostiolar tissues and exudates. Syconia samples of F. enormis were processed and stained according to the usual techniques in plant anatomy. The morphological analysis revealed different types of bracts, one type specialized in secretion, another showing transitional characteristics between secretory and non-secreting bracts, and a third one being non-secreting. They are designated as secretory ostiolar bracts, transitional bracts and wall bracts. The floral bracteoles, digital-shaped colleters present in the ostiole, at the syconium axis and at the flower receptacle, were also analyzed. All have similar structure, like finger-shaped secretory trichomes. The colleters present among ostiolar bracts may contribute to production and composition of the ostiole exudate.     

Hypochlorous acid-induced heme degradation from lactoperoxidase as a novel mechanism of free iron release and tissue injury in inflammatory diseases

Lactoperoxidase (LPO) is the major consumer of hydrogen peroxide (H(2)O(2)) in the airways through its ability to oxidize thiocyanate (SCN(-)) to produce hypothiocyanous acid, an antimicrobial agent. In nasal inflammatory diseases, such as cystic fibrosis, both LPO and myeloperoxidase (MPO), another mammalian peroxidase secreted by neutrophils, are known to co-localize. The aim of this study was to assess the interaction of LPO and hypochlorous acid (HOCl), the final product of MPO. Our rapid kinetic measurements revealed that HOCl binds rapidly and reversibly to LPO-Fe(III) to form the LPO-Fe(III)-OCl complex, which in turn decayed irreversibly to LPO Compound II through the formation of Compound I. The decay rate constant of Compound II decreased with increasing HOCl concentration with an inflection point at 100 μM HOCl, after which the decay rate increased. This point of inflection is the critical concentration of HOCl beyond which HOCl switches its role, from mediating destabilization of LPO Compound II to LPO heme destruction. Lactoperoxidase heme destruction was associated with protein aggregation, free iron release, and formation of a number of fluorescent heme degradation products. Similar results were obtained when LPO-Fe(II)-O(2), Compound III, was exposed to HOCl. Heme destruction can be partially or completely prevented in the presence of SCN(-). On the basis of the present results we concluded that a complex bi-directional relationship exists between LPO activity and HOCl levels at sites of inflammation; LPO serve as a catalytic sink for HOCl, while HOCl serves to modulate LPO catalytic activity, bioavailability, and function.     

T Cell Activation and Cytokine Profile of Tuberculosis and HIV-Positive Individuals during Antituberculous Treatment and Efavirenz-Based Regimens

Introduction

The profile of immune activation markers in tuberculosis and HIV-infected patients is already known. The impact of simultaneous infections on the immune parameters is still not fully explored.

Methods

We conducted a prospective study to estimate trajectories of activated T cell subsets and the profile of anti- and pro-inflammatory cytokines in a group of HIV-TB individuals, previously naïve for HAART, recruited from a randomized clinical trial during TB treatment and first antiretroviral therapy with efavirenz. Patients were evaluated according to the immunosuppression levels at baseline as group 1 (CD4<200 cells/mm³) and group 2 (CD4>200 cells/mm³). These parameters were measured at the time of HAART initiation (started about 30 days after the onset of TB treatment) and at the follow-up visits after 30, 60, 90 and 180 days. Trajectories were estimated using least squares estimates of the coefficients of a restricted cubic spline function in time after adjusting for subject effects, bootstrapping it 500 times.

Results

Increase of CD4 T cell counts and suppression of HIV viral load were observed for all patients under HAART and TB treatment. Descendent trajectories were observed for the activated CD8⁺/CD38⁺ and CD3⁺/HLA-DR⁺ T cell subsets, and for plasma concentration of gamma- interferon (IFN-γ). Except for TNF-α and IL-2 discrete variations were observed for the other cytokines. Differences in the trajectories of these parameters were observed for groups 1 and 2. Higher values of IFN-γ, IL-2, IL-6 and IL-10 were observed for group 1 from the baseline to two months after treatment initiation, whereas reduced levels of TNF-α were observed for this group between 60 and 120 days of HAART.

Conclusion

Independent of the immunosuppression profile at baseline, HIV-TB patients under HAART were able to recover the CD4⁺ T cell counts, and control viral replication and immune activation parameters over time.