The Brabant study: design of a large prospective perinatal cohort study among pregnant women investigating obstetric outcome from a biopsychosocial perspective.

Background: Pregnancy is characterised by many biological and psychosocial changes. Adequate maternal thyroid function is important for the developing fetus throughout gestation. Latent class analyses recently showed three different patterns of change in thyroid function throughout pregnancy with different associations with obstetric outcome.

Effect of age and gender on reference intervals of red blood cell distribution width (RDW) and mean red cell volume (MCV).

Background: Red blood cell distribution width (RDW) was recently shown to be age-dependent when using Sysmex XE-2100 hematology analyzers. As measuring RDW is subject to technology, we have investigated if this relation also exists when using a different hematology analyzer, Abbott CELL-DYN Sapphire. In addition, as RDW is generally expressed relative to mean red blood cell volume (MCV), we have explored how MCV influences the age-dependency of RDW.

The HAPPY study (Holistic Approach to Pregnancy and the first Postpartum Year): design of a large prospective cohort study.

Background: The HAPPY study is a large prospective longitudinal cohort study in which pregnant women (N ≈ 2,500) are followed during the entire pregnancy and the whole first year postpartum. The study collects a substantial amount of psychological and physiological data investigating all kinds of determinants that might interfere with general well-being during pregnancy and postpartum, with special attention to the effect of maternal mood, pregnancy-related somatic symptoms (including nausea and vomiting (NVP) and carpal tunnel syndrome (CTS) symptoms), thyroid function, and human chorionic gonadotropin (HCG) on pregnancy outcome of mother and foetus.

Methods/design: During pregnancy, participants receive questionnaires at 12, 22 and 32 weeks of gestation.

Age- and gender-specific brain natriuretic peptide (BNP) reference ranges in primary care.

Background: Chronic heart failure is a common disease with a high morbidity and mortality. In primary care, brain natriuretic peptide (BNP) is used for excluding heart failure. The Dutch and European Society of Cardiology heart failure guidelines apply two BNP cut-off levels without making distinction for gender and age.

Reference values of fetal erythrocytes in maternal blood during pregnancy established using flow cytometry.

The aim of our study was to assess the fetal RBC count in maternal blood during uncomplicated pregnancies from 26 weeks onward. We used a flow cytometric method specifically designed for use in a routine hematology analyzer. Pregnant women were recruited through midwives.

Safety of glucocorticoids can be improved by lower yet still effective dosages of liposomal steroid formulations in murine antigen-induced arthritis: comparison of prednisolone with budesonide.

Unlabelled: The goal of this study was to compare the effects of liposomal and free glucocorticoid formulations on joint inflammation and activity of the hypothalamic-pituitary-adrenal (HPA) axis during experimental antigen-induced arthritis (AIA). A dose of 10mg/kg liposomal prednisolone phosphate (PLP) gave a suppression of the HPA-axis, as measured by plasma corticosterone levels in mice with AIA and in naïve mice. In a subsequent dose-response study, we found that a single dose of 1mg/kg liposomal prednisolone phosphate (PLP) was still equally effective in suppressing joint inflammation as 4 repeated once-daily injections of 10mg/kg free PLP.

Elevated fibroblast growth factor 23 levels in a newborn with secondary hypoparathyroidism.

Fibroblast growth factor 23 (FGF-23) is a recently identified hormone that is of prime importance for phosphate homeostasis in humans. FGF-23 is secreted by osteocytes in response to phosphate-loading. It stimulates renal phosphate excretion and suppresses the formation of 1.

Fcgamma receptors directly mediate cartilage, but not bone, destruction in murine antigen-induced arthritis: uncoupling of cartilage damage from bone erosion and joint inflammation.

Objective: To determine the relationship between synovial inflammation and the concomitant occurrence of cartilage and bone erosion during conditions of variable inflammation using various Fcgamma receptor knockout (FcgammaR(-/-)) mice.

Methods: Antigen-induced arthritis (AIA) was introduced in the knee joints of various FcgammaR(-/-) mice and wild-type controls. Joint inflammation and cartilage and bone destruction levels were determined by histologic analysis.

The functional variant of the inhibitory Fcgamma receptor IIb (CD32B) is associated with the rate of radiologic joint damage and dendritic cell function in rheumatoid arthritis.

Objective: Fcgamma receptors (FcgammaRs) recognize immune complexes (ICs) and coordinate the immune response by modulating the functions of dendritic cells (DCs). The purpose of this study was to unravel the role of the inhibitory FcgammaRIIb in rheumatoid arthritis (RA) by studying the effect of the FCGR2B 695T>C polymorphism on susceptibility to RA, severity of the disease, and DC function.

Methods: Genotyping was performed in RA patients (n = 246) and healthy blood donors (n = 269).

NADPH-oxidase-driven oxygen radical production determines chondrocyte death and partly regulates metalloproteinase-mediated cartilage matrix degradation during interferon-gamma-stimulated immune complex arthritis.

In previous studies we have found that FcgammaRI determines chondrocyte death and matrix metalloproteinase (MMP)-mediated cartilage destruction during IFN-gamma-regulated immune complex arthritis (ICA). Binding of immune complexes (ICs) to FcgammaRI leads to the prominent production of oxygen radicals. In the present study we investigated the contribution of NADPH-oxidase-driven oxygen radicals to cartilage destruction by using p47phox-/- mice lacking a functional NADPH oxidase complex.

Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte death and matrix-metalloproteinase-mediated cartilage matrix degradation despite enhanced joint inflammation.

During immune-complex-mediated arthritis (ICA), severe cartilage destruction is mediated by Fcgamma receptors (FcgammaRs) (mainly FcgammaRI), cytokines (e.g. IL-1), and enzymes (matrix metalloproteinases (MMPs)).

The inhibitory receptor FcgammaRII reduces joint inflammation and destruction in experimental immune complex-mediated arthritides not only by inhibition of FcgammaRI/III but also by efficient clearance and endocytosis of immune complexes.

Studies of FcgammaRII-/- mice identified the inhibitory function of this receptor in joint inflammation and cartilage destruction induced with immune complexes (ICs). To extend our insight in the role of FcgammaRII in arthritis, we explored the role of FcgammaRII in the absence of activating receptors I and III using FcgammaRI/III-/- as well as FcgammaRI/II/III-/- mice. When antigen-induced arthritis (AIA) was elicited, which is a mixture of T cell and IC-driven inflammation, arthritis was almost absent at day 7 in FcgammaRI/III-/- mice.

FcgammaRI up-regulation induced by local adenoviral-mediated interferon-gamma production aggravates chondrocyte death during immune complex-mediated arthritis.

Using various FcgammaR-deficient mice, we have obtained suggestive evidence that FcgammaRI on macrophages is responsible for severe cartilage destruction during arthritis mediated by immune complexes (ICs). This role of FcgammaRI is pronounced in the presence of activated Th1 cells and a likely Th1 cell-derived cytokine mediating up-regulation of FcgammaRI expression is interferon (IFN)-gamma. We now investigated whether local overexpression of IFN-gamma using an adenoviral vector is able to elevate cartilage destruction during experimental immune complex-mediated arthritis (ICA) and to what extent this process is FcgammaRI-mediated.