Luc J I Zimmermann

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

Are you Luc J I Zimmermann?

Claim your profile

Publications (89)335.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Acute respiratory distress syndrome (ARDS) is a life-threating condition with high morbidity and mortality. Inflammation is the main factor in the pathogenesis of ARDS. Therefore systemic corticosteroids are a rational therapeutic approach, but the effect of corticosteroids is still unclear. In this study, we looked at the effects of corticosteroids in ventilated sheep with ARDS, induced by lung lavage. Methods We performed a prospective, randomised study in 64 ventilated sheep with ARDS, to evaluate the effect of corticosteroids and oxygen concentration on gas exchange and lung injury. Oxygenation index (OI) and ventilation efficacy index (VEI) were calculated to evaluate gas exchange. Lung injury was assessed by inflammatory response in broncho-alveolar lavage fluid (BALF) and plasma and histology of the lung. Results OI, VEI, lung inflammation, surfactant production, or lung histology was not influenced by corticosteroids. In the 100 % oxygen groups, OI was higher and total number of cells and disaturated phospholipids were lower in BALF. Conclusion Our study showed that corticosteroids did not influence inflammation in early phase ARDS and that hyperoxia aggravated lung injury which could not be modulated by dexamethasone in early phase ARDS.
    Beiträge zur Klinik der Tuberkulose 12/2014; · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite efforts to reduce mortality caused by stroke and perinatal asphyxia, these are still the 2(nd) largest cause of death worldwide in the age groups they affect. Furthermore, survivors of cerebral hypoxia-ischemia often suffer neurological morbidities. A better understanding of pathophysiological mechanisms in focal and global brain ischemia will contribute to the development of tailored therapeutic strategies. Similarly, insight in molecular pathways involved in preconditioning-induced brain protection will provide possibilities for future treatment. Microarray technology is a great tool for investigating large scale gene expression, and has been used in many experimental studies of cerebral ischemia and preconditioning to unravel molecular (patho-) physiology. However, the amount of data across microarray studies can be daunting and hard to interpret which is why we aim to provide a clear overview of available data in experimental rodent models. Findings for both injurious ischemia and preconditioning are reviewed under separate subtopics such as cellular stress, inflammation, cytoskeleton and cell signaling. Finally, we investigated the transcriptome signature of brain protection across preconditioning studies in search of transcripts that were expressed similarly across studies. Strikingly, when comparing genes discovered by single-gene analysis we observed only 15 genes present in two studies or more. We subjected these 15 transcripts to DAVID Annotation Clustering analysis to derive their shared biological meaning. Interestingly, the MAPK signaling pathway and more specifically the ERK1/2 pathway geared toward cell survival/proliferation was significantly enriched. To conclude, we advocate incorporating pathway analysis into all microarray data analysis in order to improve the detection of similarities between independently derived datasets.
    Brain research 04/2014; · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The umbilical cord (UC) is a promising source of mesenchymal stromal cells (MSCs). UC-MSCs display very similar in vitro characteristics to bone marrow-MSCs and could represent a valuable alternative for cell-based therapies. However, it is still unclear whether UC-MSCs are prone or not to the acquisition of genomic imbalances during in vitro expansion. With the use of array-comparative genomic hybridization, we compared copy number variations of early (P2-P3) and late (>P5) passages of in vitro-expanded UC-MSCs. In two of 11 long-term UC-MSCs cultures, we observed the appearance of clones carrying genomic imbalances, which generated genetic mosaicism at intermediate passages. Although still able to reach the senescence phase, the cells carrying the genomic imbalance acquired a proliferative advantage, as demonstrated by the increase in frequency during long-term culture. Altogether, our results suggest that UC-MSC-based clinical protocols should be designed with caution; their clinical use should be preceded by array-comparative genomic hybridization screening for the acquisition of genomic imbalances during in vitro expansion.
    Cytotherapy 11/2013; 15(11):1362-1373. · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.
    Neonatology 05/2013; 104(1):49-55. · 2.57 Impact Factor
  • Jasper V Been, Luc J I Zimmermann, Boris W Kramer
    The Journal of pediatrics 01/2013; · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Late preterm deliveries (LP, between 34-36 wks), have considerably increased in the last decades. About 20-25% of LP infants require intensive care and morbidity on public health is of great magnitude. Therefore, we aimed at offering a reference curve in LP period of a well-established neurotrophic and brain damage marker namely S100B protein. METHODS: We collected, between December 2009 and March 2012, urine samples, at first void (within 6-hours from birth) for S100B assessment, in 277 healthy LP infants consecutively admitted to our units. Standard clinical and laboratory monitoring parameters were also recorded. S100B was measured by a using a commercially available immunoluminometric assay. RESULTS: S100B pattern in LP infants was characterized by a slight decrease in protein's concentration from 34 to 35 wks. From 35 wks onwards S100B started to increase reaching a significant difference (P=0.008) at 36 wks. When corrected for gender, significant higher (P<0.01, for all) S100B concentrations in female were observed from 34 to 36 wks. Polynomial type-1 regression analysis showed a significant correlation (R=-0.05; P<0.001) between gestational age and S100B in LP infants both considering the whole study population or when corrected for gender. CONCLUSIONS: S100B in LP infants is gestational age and gender dependent. The present reference curve, for S100B in LP period, offers additional support to protein's neurotrophic role and suggests that gestational age and gender has to be taken into the due account, whenever S100B is measured, in order to avoid bias factors.
    Clinica chimica acta; international journal of clinical chemistry 12/2012; · 2.54 Impact Factor
  • R M J Moonen, C G A Kessels, L J I Zimmermann, E Villamor
    [Show abstract] [Hide abstract]
    ABSTRACT: Infants with intrauterine growth retardation are prone to intestinal disorders. The morphological and molecular mechanisms that lead to these complications are not completely understood and suitable experimental models are necessary. The aim of this study was to characterize mesenteric artery (MA) reactivity, small intestine morphometry and intestinal expression of vascular endothelial growth factor (VEGF) in a chicken model of hypoxia-induced fetal growth restriction. Chicken embryos (15 and 19 incubation days) and hatchlings (<3-h-old and 1-d-old) were incubated under hypoxic (15% O(2) from day 0 to day 19 of incubation) or normoxic conditions. Vascular reactivity was studied using wire miography. Intestinal morphometry was assessed in hematoxyline-eosine-stained sections. VEGF mRNA expression was determined by RT-PCR analysis. Hypoxia increased the responsiveness of chicken embryo MAs to the adrenergic agonist norepinephrine, the polypeptide endothelin (ET)-1, and the nitric oxide donor sodium nitroprusside and decreased the responsiveness to the endothelium-dependent relaxant agonist acetylcholine. However, the majority of these alterations, with the exception of the hyperresponsiveness to ET-1, were not present in the hypoxic hatchlings. When intestinal histology was analyzed, subtle hypoxia-induced changes were noted in the villi and the muscularis propria from the hatchlings. Hypoxic incubation also diminished the expression of VEGF mRNA in the terminal ileum of the hatchlings. In conclusion, chronic moderate hypoxia during incubation results in subtle but significant alterations in chicken MAreactivity, small intestine morphology and VEGF expression. Whether these alterations may have a direct effect on the functional status of the intestine remains to be investigated.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2012; 63(6):601-12. · 2.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Recruitment manoeuvres are widely used in clinical practice to open the lung and prevent lung injury by derecruitment, although the evidence is still discussed. In this study two different recruitment manoeuvres were compared to no recruitment manoeuvres (control) in ventilated sheep with acute respiratory distress syndrome (ARDS), induced by lung lavage. METHODS: We performed a prospective, randomised study in 26 ventilated sheep with ARDS, to evaluate the effect of two different recruitment manoeuvres on gas exchange, blood pressure and lung injury. The two different recruitment manoeuvres, the high pressure recruitment manoeuvre (HPRM), with high peak pressure, and the smooth and moderate recruitment manoeuvre (SMRM), with lower peak pressure, were compared to controls (no recruitment) after disconnection. Oxygenation index and ventilation efficacy index were calculated to evaluate gas exchange. Lung injury was assessed by inflammatory response in broncho-alveolar lavage fluid (BALF) and blood and histology of the lung. RESULTS: Oxygenation index improved significantly after both recruitment manoeuvres compared with controls, but no significant difference was found between the recruitment manoeuvres. Blood pressure decreased after HPRM but not after SMRM. HPRM induced a higher number of total cells and more neutrophils in the BALF. In the histology of the lung, mean alveolar size was increased in the dorsocranial region of the lung of SMRM compared to controls. CONCLUSION: Recruitment manoeuvres improved oxygenation, but SMRM was superior, with respect to hemodynamics and pulmonary inflammation, in ventilated sheep suffering from ARDS induced by lung lavage.
    Beiträge zur Klinik der Tuberkulose 11/2012; · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Restoring the barrier integrity of the alveolar epithelium after injury is pivotal. In the current study, we evaluated the effects of surfactant, surfactant protein A (SP-A), transforming growth factor β (TGF-β), and analogues of SP-A on alveolar epithelial repair. Additionally, we assessed the influence of microvascular endothelial cells on reepithelialization. METHODS: Repair was studied in an in vitro model system consisting of a bilayer coculture of A549 and human pulmonary microvascular endothelial cells (HPMECs), which stably expressing fluorescent proteins. The epithelial repair was assessed in a scratch assay using vital fluorescence microscopy and compared with a monolayer of A549 cells. RESULTS: HMPEC cells differentially modulated the response of the A549 cells. Surfactant and SP-A augmented the reepithelialization in the presence of HPMECs, whereas in the absence of HPMECs, surfactant inhibited wound healing and SP-A failed to alter the response. Like SP-A, a structural analogue of its collagenous tail domain augmented the reepithelialization in the model system, whereas an analogue of its head domain did not alter the response. Additionally, we demonstrated that TGF-β associated with SP-A was able to initiate the Smad-dependent TGF-β pathway and that both TGF-β and TGF-β free SP-A were able to stimulate wound healing in the bilayer model. CONCLUSIONS: These data show that surfactant, SP-A and TGF-β, influence epithelial repair in vitro and that the microvascular endothelial cells can modulate the response. This indicates that surfactant and SP-A could play a role in alveolar epithelial repair and that the microvascular endothelium may be involved in these processes.
    Beiträge zur Klinik der Tuberkulose 10/2012; · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process.
    Experimental Cell Research 09/2012; · 3.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To accumulate available evidence regarding the association between antenatal inflammation and necrotizing enterocolitis (NEC). STUDY DESIGN: A systematic literature search was performed using Medline, Embase, Cochrane Library, ISI Web of Knowledge, and reference hand searches. Human studies published in English that reported associations between chorioamnionitis or other indicators of antenatal inflammation and NEC were eligible. Relevant associations were extracted and reported. Studies reporting associations between histological chorioamnionitis (HC) and NEC, HC with fetal involvement and NEC, and clinical chorioamnionitis and NEC were pooled in separate meta-analyses. RESULTS: A total of 33 relevant studies were identified. Clinical chorioamnionitis was significantly associated with NEC (12 studies; n = 22 601; OR, 1.24; 95% CI, 1.01-1.52; P = .04; I(2) = 12%), but the association between HC and NEC was not statistically significant (13 studies; n = 5889; OR, 1.39; 95% CI, 0.95-2.04; P = .09; I(2) = 49%). However, HC with fetal involvement was highly associated with NEC (3 studies; n = 1640; OR, 3.29; 95% CI, 1.87-5.78; P ≤ .0001; I(2) = 10%). Selection based on study quality did not affect the results. No indications of publication bias were apparent. Multivariate analyses in single studies generally attenuated the reported associations. Several associations between other markers of antenatal inflammation and NEC are reported. CONCLUSION: Currently available evidence supports a role for antenatal inflammation in NEC pathophysiology. This finding emphasizes the need to further study the underlying mechanisms and evaluate potential interventions to improve postnatal intestinal outcomes.
    The Journal of pediatrics 08/2012; · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND/AIMS: To investigate whether short-term changes in body composition as a result of growth hormone therapy could be used to predict its growth effect after 1 year in children with growth hormone deficiency (GHD) and children born small for gestational age (SGA). MetHODS: 88 GHD children and 99 SGA children who started treatment with recombinant human growth hormone were included. Total body water (TBW) and height were measured. After 1 year, patients were divided into adequate and inadequate responders. ResuLTS: In GHD and SGA children a sensitivity of 87 and 53%, respectively, and a specificity of 58 and 83%, respectively, were found. The positive predictive values for GHD and SGA children were 73 and 90%, respectively. The negative predictive values were 75 and 32%, respectively. CONCLUSION: Changes in body composition data measured by TBW are a valuable tool to correctly predict 75% of the GHD children and are only useful in SGA children when the change in TBW is above the cut-off value of 0.7 l/m(2).
    Hormone Research in Paediatrics 07/2012; 78(1):18-23. · 1.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chorioamnionitis is a major risk factor for preterm birth in multifetal pregnancies. However, there is little clinical data whether chorioamnionitis is restricted to one amniotic compartment in multifetal pregnancies. To explore whether chorioamnionitis is confined to the exposed compartment and does not cross to the unaffected fetus in twin pregnancy. In twin pregnant sheep, one of the twins was exposed to either 2 or 14 days of intra-amniotic lipopolysaccharide (LPS) while the co-twin was exposed to either 2 or 14 days of intra-amniotic saline (n = 3 for each exposure). Singletons were included in this study to compare the grade of inflammation with twins. All fetuses were delivered at 125 days of gestation (term = 150 days). Chorioamnionitis was confirmed by histological examination. Lung inflammation was assessed by cell count in bronchoalveolar lavage. Lung compliance was assessed at 40 cm H(2)O. Results were compared using analysis of variance (ANOVA) with a post-hoc Tukey analysis. Inflammation in placenta, membranes and lung of LPS-exposed twins was significantly higher after 2 and 14 days of exposure when compared to the saline-exposed co-twins. Lung compliance in LPS-exposed twins was significantly increased after 14 days when compared to saline-exposed co-twins. Intrauterine LPS exposure increased lung compliance and inflammation in the membranes, placenta and lung to the same extent in twins as in singletons. In twin pregnant sheep, inflammation of the membranes, placenta and fetal lung was strictly limited to the exposed fetus in the amniotic compartment in which the LPS was injected.
    Neonatology 05/2012; 102(2):81-8. · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Underdiagnosis and low levels of asthma control are frequent occurring problems in patients with asthma. The study aim was to evaluate the ability of non-invasive inflammatory markers in exhaled breath to predict exacerbations of childhood asthma, and to assess the time course of changes in these exhaled markers before, during and after exacerbations. The design was a prospective one-year longitudinal study. Regular two-month visits at the outpatient clinic were performed. Forty children with asthma (aged 6-16 years) participated. The primary outcome measure was the occurrence of an exacerbation. Assessment was made of the presence and severity of pulmonary symptoms, use of medication, and measurements of forced expiratory volume in 1 s using home monitor. The following independent parameters were assessed during outpatient visits: (1) exhaled nitric oxide, (2) inflammatory markers in exhaled breath condensate: acidity, nitrite, hydrogen peroxide, interleukin-1α, -5, -13, interferon-γ, (3) lung function, (4) asthma control score. Thirty-eight of 40 children completed the study. Sixteen children developed exacerbations, of which ten were moderate and six severe. Univariate Cox regression analysis revealed that condensate acidity, interleukin-5 and asthma control score were significant predictors of an asthma exacerbation (P < 0.05). In the multivariate Cox regression analysis, exacerbations were best predicted by the asthma control score and by the level of interleukin-5 in exhaled breath condensate (Wald scores of 7.19 and 4.44, P = 0.007 and P = 0.035 respectively). The predicted survival curve of this multivariate model showed a two times reduced risk on exacerbations in the category of children with the 10% most optimal values of IL-5 and asthma control score. Both exhaled breath condensate interleukin-5 level and asthma control score were significant predictors of asthma exacerbations. These findings open up the possibility of assessing the potential of such parameters to titrate asthma treatment in future studies.
    Clinical & Experimental Allergy 05/2012; 42(5):792-8. · 4.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antenatal exposure of the fetus to inflammation may alter postnatal organ development. In our previous work, we demonstrated that the fetal liver is involved in the systemic inflammation associated with chorioamnionitis, leading to metabolic changes. On the basis of these findings, we hypothesized that chorioamnionitis can lead to postnatal inflammation-related liver injury and disturbed lipid metabolism. Chorioamnionitis was induced in sheep by intra-amniotic injection of lipopolysaccharide (LPS) or saline at 90, 100 and 110 days of gestation. Liver homeostasis and lipid metabolism were analyzed at term and at 7 weeks of age. At term, hepatic T-lymphocytes and apoptotic hepatocytes were increased. In addition, hepatic cholesterol and triglyceride levels were decreased in LPS-exposed animals compared with controls. At 7 weeks of age, no hepatic inflammation could be detected. However, liver triglycerides and plasma cholesterol levels were increased in LPS-exposed animals relative to controls. The changes in lipid levels at 7 weeks of age were associated with increased leptin receptor mRNA levels, increased lipid peroxidation, increased expression of cytochrome c oxidase subunit 4 as a marker for mitochondrial function and increased circulating ceramide levels. These findings demonstrate that chorioamnionitis-mediated antenatal inflammation-related liver disturbances have long-lasting postnatal effects on lipid metabolism.
    Journal of Developmental Origins of Health and Disease. 04/2012; 3(02).
  • [Show abstract] [Hide abstract]
    ABSTRACT: We were able to demonstrate the presence of transforming growth factor β1 and transforming growth factor β2 (TGF-β1,2) in human as well as porcine pulmonary surfactants and SP-A purified from these surfactants. Human SP-A contained 480±74 pg TGF-β1 and 61±16 pg TGF-β2 per mg SP-A and human pulmonary surfactant contained 140±28 pg TGF-β1 and 67±13 TGF-β2 per mg protein. Porcine SP-A contained 306±46 pg TGF-β1 and 43±12 pg TGF-β2 per mg SP-A and porcine pulmonary surfactant contained 75±18 pg TGF-β1 and 22±13 TGF-β2 per mg protein. Size-exclusion chromatography indicated binding of TGF-β1,2 to SP-A. Deglycosylation of SP-A released TGF-β1,2 from SP-A indicating a role for the carbohydrate moieties of SP-A in binding of TGF-β1,2. TGF-β-free SP-A was obtained by incubating SP-A with 5 mM deoxycholate at pH 9.2 followed by size-exclusion chromatography, a protocol which can be used to study the biological activities of SP-A and TGF-β1,2 separately. In addition, we demonstrated that after incubation of SP-A with TGF-β1,2, only a part of the added TGF-β1,2 can be measured, whereas after acid treatment almost all added TGF-β1,2 was determined, suggesting that complex formation between SP-A and TGF-β1,2 influences the measurements of TGF-β1,2 in biological samples.
    Journal of immunological methods 01/2012; 375(1-2):111-7. · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: S100B protein is a well-established marker of brain damage. Its importance in urine assessment is the convenience of a collection and sampling procedure that can be repeated without risk for the newborn. Since S100B is mainly eliminated by the kidneys and perinatal asphyxia (PA) is often associated with kidney failure we investigated whether S100B release might be kidney-mediated, thereby modifying the protein's reliability as a brain-damage marker. We examined a cohort of healthy (n=432) and asphyxiated newborns (n=32) in whom kidney function parameters (blood urea and creatinine concentrations and urine gravity) and urine S100B concentrations were assessed in the first hours after birth. Data were analyzed by multiple logistic regression analysis with S100B as independent variable among a variety of clinical and laboratory monitoring parameters. S100B urine concentrations were significantly higher (P<0.01) in PA newborns than controls. No significant correlations (P>0.05, for all) between total urine S100B levels and kidney function parameters such as creatinine (r=0.03), urea (r=0.04) and urine gravity (r=0.06) were found. Multiple logistic regression analysis of a series of clinical and laboratory monitoring parameters (odds ratio at sampling: 9.47) with S100B as independent variable showed a positive significant correlation only between S100B levels (P<0.001) and the occurrence of PA. The present study shows that altered kidney function is not an adverse and/or confounding factor in urine S100B assessment and marks a new step towards the introduction of longitudinal monitoring of brain constituents in clinical practice.
    Clinica chimica acta; international journal of clinical chemistry 01/2012; 413(1-2):150-3. · 2.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Infections during pregnancy can adversely affect the development of the fetal brain. This may contribute to disease processes such as schizophrenia in later life. Changes in the (cyto-) architecture of the anterior cingulate cortex (ACC), particularly in GABA-ergic interneurons, play a role in the pathogenesis of schizophrenia. We hypothesized that exposure to infection during pregnancy could result in cyto-architectural changes in the fetal ACC, similar to the pathogenesis seen in schizophrenia. Fetal sheep of 110 days GA (term=150 days GA) received an intravenous injection of 100 ng or 500 ng lipopolysaccharide (LPS) or saline as control. After delivery at 113 days GA, the cyto-architecture of the cingulate cortex (CC) was examined by immunohistochemistry. High dose LPS exposure resulted in a decreased density of GFAP-, calbindin D-28K- and parvalbumin-immunoreactive cells in the CC. In addition, these cells and calretinin-immunoreactive cells showed a changed morphology with reduced cell processes. This study provides further evidence that intra-uterine endotoxemia can induce changes in the fetal brain which correspond with changes seen in schizophrenia.
    Frontiers in bioscience (Elite edition) 01/2012; 4:2845-53.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Histological chorioamnionitis (HC) is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns. Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF) in preterm newborns. Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤32.0 weeks) born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216) or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206). HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth. HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92-0.98), a positive predictive value of 80% (95%CI = 74-84%), and a negative predictive value of 93% (95%CI = 88-96%). Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88-0.96), positive predictive value 59% (95%CI = 52-62%), and negative predictive value 97% (95%CI = 93-99%). External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values. Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation.
    PLoS ONE 01/2012; 7(10):e46217. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Asphyctic preconditioning is thought to attenuate the cellular stress response which reduces brain damage.
    Pediatric Research 11/2011; · 2.67 Impact Factor

Publication Stats

810 Citations
335.66 Total Impact Points


  • 2013
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 2004–2013
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2004–2012
    • Maastricht University
      • • Kindergeneeskunde
      • • Department of Pediatrics
      Maastricht, Provincie Limburg, Netherlands
  • 2011
    • Artemisia Fetal–Maternal Medical Centre
      Roma, Latium, Italy
  • 2010
    • Spaarne Ziekenhuis
      • Department of Pediatrics
      Hoofddorp, North Holland, Netherlands
  • 2002–2004
    • University of Padova
      • Department of Pediatrics
      Padova, Veneto, Italy
  • 1996–2003
    • Erasmus Universiteit Rotterdam
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands