Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies.

BACKGROUND: Enterocyte damage is the hallmark of coeliac disease (CD) resulting in malabsorption. Little is known about the recovery of enterocyte damage and its clinical consequences. Serum intestinal fatty acid binding protein (I-FABP) is a sensitive marker to study enterocyte damage. AIMS: To evaluate the severity of enterocyte damage in adult-onset CD and its course upon a gluten-free diet (GFD). Furthermore, the correlation among enterocyte damage, CD autoantibodies and histological abnormalities during the course of disease is studied. METHODS: Serum I-FABP levels were determined in 96 biopsy-proven adult CD patients and in 69 patients repeatedly upon a GFD. A total of 141 individuals with normal antitissue transglutaminase antibody (IgA-tTG) levels served as controls. I-FABP levels were related to the degree of villous atrophy (Marsh grade) and IgA-tTG. RESULTS: I-FABP levels were elevated in untreated CD (median 691 pg/mL) compared with controls (median 178 pg/mL, P < 0.001) and correlated with Marsh grade (r = 0.265, P < 0.05) and IgA-tTG (r = 0.403, P < 0.01). Upon a GFD serum levels decreased significantly, however, not within the range observed in controls, despite the common observed normalisation of IgA-tTG levels and Marsh grade. CD patients with elevated I-FABP levels nonresponding to GFD showed persistent histological abnormalities. CONCLUSIONS: Enterocyte damage assessed by serum I-FABP correlates with the severity of villous atrophy in coeliac disease at the time of diagnosis. Although enterocyte damage improves upon treatment, substantial enterocyte damage persists despite absence of villous atrophy and low IgA-tTG levels in the majority of cases. Elevated I-FABP levels nonresponding to gluten-free diet are indicative of histological abnormalities and warrant further evaluation.

The visually-evoked cerebral blood flow response in women with a recent history of preeclampsia and/or eclampsia.

Several studies provide evidence for altered cerebral hemodynamics during (pre)eclampsia. Whether (pre)eclampsia has a persistent negative impact on cerebral hemodynamics, possibly contributing to an elevated risk of premature stroke, is unknown. The aims of this study were (i) to refine and apply a control system-based method previously introduced by Rosengarten to quantify the visually-evoked blood flow response of the posterior cerebral artery (PCA); and (ii) to test the hypothesis with this method that cerebral hemodynamics in women with a recent history of (pre)eclampsia is abnormal relative to that in parous controls. Hereto, we recorded cerebral blood flow velocity (CBFV) in the PCA by transcranial Doppler (TCD) sonography during cyclic visual stimulation in 15 former preeclamptics, 13 former eclamptics and 13 controls. The typical CBFV response was fitted with the step response of a second-order-linear model enabling quantification by parameters K (gain), zeta (damping), omega (natural frequency), T(v) (rate time) and T(d) (time delay). The method refinement introduced here consisted of response filtering before quantification and of considering the individual instead of group-averaged response patterns. Application of this refinement reduced the fitting errors (1.4 +/- 1.2 vs. 3.2 +/- 1.8, p < 0.01). Intergroup differences in model parameters were not found. Although statistically not significant, a trend was observed that critical damping (zeta>1) occurred more frequently in the combined group of former patients than in the controls (7 of 28 vs.1 of 13, p = 0.16). Critical damping (zeta>1) reflects an abnormal response, which is either compensated for by a rise in rate time ("intermediate"; zeta>1; T(v) > 20) or remains uncompensated ("sluggish"; zeta>1; T(v) < 20). Critical damping increased significantly (p = 0.039) with (pre-)eclampsia-to-test-interval in the PE+E patients with abnormal responses (zeta>1), suggesting that (pre)eclampsia might induce diminishing cerebral hemodynamic function over time. Based on a system-analytical classification approach, the data of this study provide evidence for individual CBFV responses to be abnormal in former (pre)eclamptics compared with controls. Further study is needed to reveal how the abnormal CBFV response classification reflects cerebrovascular dysfunction.