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Biomedical subjects

Olaf Dammann

Publications and source records attributed to Olaf Dammann.

At least 19 recordsLinked to original sources
PubMed2005

Protein detection in dried blood by surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS).

BACKGROUND: The rapid and reliable identification of biomarkers in the smallest possible amount of blood remains a challenge in biomarker epidemiological research involving preterm newborns. OBJECTIVE: We wanted to explore whether the proteomics approach of 'surface-enhanced laser desorption/ionization-time of flight mass spectrometry' (SELDI-TOF MS) is possible and feasible in whole cord blood previously dried on filter paper. METHODS: Umbilical cord blood from 7 healthy newborns was frozen as serum, whole blood (with or without additives), or dried on filter paper (with or without additives). We used the SELDI-TOF MS technique for protein detection on the ProteinChip arrays: weak cationic exchange array (CM10), hydrophobic array (H50), and strong anion exchange array (Q10). Profiles were compared in terms of peak intensity and number of resolved peaks. RESULTS: Dried neonatal blood, eluted from filter paper, revealed profiles similar to the profiles derived from serum at a protein range of 3-10 kDa. Among additives, heparin led to highest peak intensities for both blood and dried blood. Spectra from heparinized whole blood and heparinized dried blood from the umbilical cord of 8 different healthy newborns on three different types of ProteinChip arrays were very similar. CONCLUSION: We conclude that it is possible and feasible to use SELDI-TOF MS for recovery and detection of whole proteins from dried blood collected on filter paper. The method is easy to perform in large groups of newborns, minimizing the amount of blood needed for biomarker studies. The validity and reproducibility of this method needs to be studied in detail.

Anticoagulants↗
PubMed2005

Association of two mutations in the CHEK2 gene with breast cancer.

The 1100delC mutation of the cell cycle checkpoint kinase 2 (CHEK2) gene confers an increased risk for breast cancer, but the clinical impact of other CHEK2 gene variants remains unclear. We determined the frequency of two functionally relevant CHEK2 gene mutations, I157T and IVS2+1G > A, in two large series of breast cancer cases and controls from two independent populations. Our first series consisted of a hospital-based cohort of 996 German breast cancer cases and 486 population controls, and the second series consisted of 424 breast cancer patients and 307 population controls from the Republic of Belarus. The missense substitution I157T was identified in 22/996 cases (2.2%) vs. 3/486 controls (0.6%; OR = 3.6, 95% CI 1.1-12.2, p = 0.044) in the German population and in 24/424 cases (5.7%) vs. 4/307 controls (1.3%; OR = 4.5, 95% CI 1.6-13.2, p = 0.005) in the Byelorussian cohorts. The splicing mutation IVS2+1G > A was infrequent in both populations, being observed in 3/996 German and 4/424 Byelorussian patients (0.3% and 0.9%, respectively) and in 1/486 German controls (0.2%; adjusted OR = 4.0, 95% CI 0.5-30.8, p = 0.273). Heterozygous CHEK2 mutation carriers tended to be diagnosed at an earlier age in both populations, but these differences did not reach statistical significance. Family history of breast cancer did not differ between carriers and noncarriers. Our data indicate that the I157T allele, and possibly the IVS2+1G > A allele, of the CHEK2 gene contribute to inherited breast cancer susceptibility.

Adult↗
PubMed2005

The adaptive immune response in neonatal cerebral white matter damage.

Hypotheses that inflammation contributes to neonatal cerebral white matter damage have evolved over the last three decades. The latest, expanded here, suggests that the adaptive immune system contributes to the intensity and duration of the processes that result in damage to cerebral white matter in the fetus and newborn. We propose several mechanisms by which fetal T lymphocytes could be activated during fetal exposure to infection. These include specific recognition of bacterial antigens, specific recognition of autoantigens, polyclonal activation by Toll-like receptors, and bystander activation by cytokines.

Adaptation, Physiological↗
PubMed2005

Magnetic resonance and ultrasound brain imaging in preterm infants.

Cranial ultrasonography has been used to identify brain injury in preterm neonates for more than two decades. More recently, magnetic resonance imaging has been used to evaluate brain development and pathology in these infants. In this review we describe how well findings from these two imaging modalities agree with histology findings and neuro-developmental outcome. In addition, we discuss studies comparing ultrasound and magnetic resonance imaging findings.

Brain Injuries↗
PubMed2005

Lung and brain damage in preterm newborns, and their association with gestational age, prematurity subgroup, infection/inflammation and long term outcome.

Compared with those born at term, preterm newborns are at an increased risk of short term disorders of the lung (bronchopulmonary dysplasia; BPD) and the brain (white matter damage; WMD), and of long term developmental and pulmonary dysfunctions. Although all of these adverse outcomes are associated with low gestational age, brain, but not lung, damage appears to be associated with the prematurity subgroup [spontaneous preterm labour and/or preterm prelabour rupture of membranes (PPROM) vs pregnancy-induced hypertension (PIH)]. Part of the association between brain damage and prematurity subgroup might be due to a differential exposure of members of these subgroups to perinatal infection/inflammation. There is a lack of studies evaluating the association of antenatal and perinatal risk factors with late childhood pulmonary dysfunction among those born during the second trimester. In this paper we discuss the complexities that paediatricians, perinatologists and perinatal epidemiologists face as they try to understand the contributions of factors associated with preterm birth to neonatal and childhood disorders.

Brain Diseases↗
PubMed2004

Lung and brain damage in preterm newborns. Are they related? How? Why?

The relationships among bronchopulmonary dysplasia (BPD), brain white matter damage (WMD) and cerebral palsy (CP) are far from simple. Apparently, BPD and WMD are not associated, while BPD and CP are. The most likely explanation for this paradox is that ultrasound imaging does not identify all the WMD that might lead to CP ('tip-of-the-iceberg effect'). We discuss further methodological inconsistencies, etiological peculiarities related to antenatal infection/inflammation, and intervention-related issues. In particular, we expand on the multiple-hit scenario in the etiology of BPD and offer support for the hypothesis that it is not lung disease, but factors associated with lung disease (e.g. postnatal steroid exposure) that increase the risk for developmental disability in childhood.

Brain Diseases↗
PubMed2004

Coagulation, inflammation, and the risk of neonatal white matter damage.

Indicators of coagulation activation are sometimes increased in the blood of newborns and adults who have a systemic inflammatory response. These coagulation factors have the ability to exacerbate inflammation, which in turn can promote coagulation. Therapies directed solely at coagulation factors and therapies directed solely at inflammation factors have not proved effective in reducing mortality in adults with a systemic inflammatory response syndrome and multi-organ dysfunction (SIRS/MOD). On the other hand, the only therapy that has reduced mortality in SIRS/MOD is activated protein C, which has both anti-coagulation and anti-inflammatory effects. This and other observations support the view that activated coagulation factors enhance inflammation. Since newborns at risk of cerebral white matter damage and cerebral palsy are more likely than their peers to have a systemic inflammatory response, which is sometimes accompanied by elevated blood levels of coagulation factors, we suggest that activated coagulation factors contribute to the occurrence of cerebral white matter damage by exacerbating inflammatory phenomena, rather than by occluding cerebral blood vessels.

Adult↗
PubMed2004

Inflammatory brain damage in preterm newborns--dry numbers, wet lab, and causal inferences.

Epidemiologic observations support the contention that infection, inflammation, and neonatal white matter damage (WMD) are associated. We also have documentation from multiple experimental models that infection/inflammation can damage developing white matter. Based on these observations in humans and animals, we offer causal inferences using widely accepted causal criteria and the multivariable model of causation. As much as we want to, however, we are reluctant to state unequivocally that inflammation causes WMD in humans born much before term. The main reason is that we lack convincing evidence that inflammation precedes WMD (temporal evidence). We also need more (and more detailed) observational studies clarifying the presumed infection --> inflammation --> WMD sequence before we can initiate intervention trials to reduce the risk of WMD.

Analysis of Variance↗
PubMed2004

Preconditioning and the developing brain.

Preconditioning occurs when a subinjurious exposure renders the brain less vulnerable to a subsequent damaging exposure. In this essay, various models of preconditioning in the immature brain are discussed. Adenosine, excitatory amino acids, nitric oxide, hypoxia-inducible factor, ATP-sensitive K+ channels, caspases, heat shock proteins, inflammatory mediators and gene expression all seem to be involved in sensing, transducing and executing preconditioning resistance. Also reviewed in this essay is evidence that some subinjurious exposures render the brain more vulnerable to a subsequent damaging exposure. We believe that unraveling the mechanisms of how the developing brain becomes inherently resilient or vulnerable will offer important insights into the pathogenesis of injury. Preconditioning of the brain or induction of tolerance of the immune system might be utilized in the future to decrease CNS vulnerability and the occurrence of perinatal brain injury.

Animals↗
PubMed2004

Impact of motor skills on cognitive test results in very-low-birthweight children.

Standardized tests that are frequently used to evaluate the cognitive development of very-low-birthweight children often appear to measure motor ability as well as cognitive skills. To estimate the impact of motor skills on individual test performance among very-low-birthweight children of kindergarten age, we employed factor analysis in a sample of 298 very-low-birthweight children that included severely disabled children. Using a test battery designed to measure concentration, language skills, overall cognitive development, visuomotor abilities, and memory, we identified two factors in each of three diagnostic subgroups: unimpaired children (n = 184), clumsy children (n = 56), and children with cerebral palsy (n = 33). Based on the pattern of factor loadings, we interpret the first factor as capturing language and overall cognitive abilities, whereas the second factor appears to capture motor abilities. Language skills explained 49% and motor abilities accounted for 16% of the overall variance of the individual test results. Among children with attention deficit (n = 25), a third factor emerged. In these children, we interpret the first factor as capturing language or cognitive skills, the second as representing visuomotor skills, and the third as a quantifier of the ability to concentrate. The test battery tested the same abilities in impaired and unimpaired children; however, these were not always the abilities that the battery aimed to test. Future studies need to evaluate whether factor scores only for cognitive but not motor abilities might be useful outcome variables.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Bronchopulmonary dysplasia is not associated with ultrasound-defined cerebral white matter damage in preterm newborns.

Bronchopulmonary dysplasia (BPD) and cerebral white matter damage (WMD) are neonatal disorders that occur most commonly in those who are born much before term. In a large multicenter database, we sought to determine whether the two disorders occur together more frequently than expected and whether BPD and other neonatal respiratory characteristics are more common among infants who develop ultrasound-defined WMD than among those who do not. In a sample of 904 infants who were born before the 30th week of gestation and survived until 36 wk postmenstrual age, we did not find a co-occurrence of BPD and WMD above what would be expected by chance. Confounding does not seem to account for this lack of association between WMD and BPD. In conclusion, our findings do not support the hypothesis that BPD contributes to the occurrence of sonographically defined WMD.

Brain Diseases↗
PubMed2003

Maternal fever at birth and non-verbal intelligence at age 9 years in preterm infants.

To test the hypothesis that characteristics of perinatal infection are associated with long-term cognitive limitations among preterm infants, we analyzed data from 294 infants (142 females, 152 males) < or = 1500 g birthweight and <37 completed weeks of gestation who were examined at age 9 years. We identified 47 children (20 females, 27 males) who had a non-verbal Kaufman Assessment Battery for Children (K-ABC) scale standard value below 70, i.e. more than 2 SDs below the age-adjusted mean. The 247 children (122 females, 125 males) with a score > or = 70 served as control participants. Maternal nationality and education, and low gestational age were significantly associated with a K-ABC non-verbal standard value <70. Both neonatal brain damage (intraventricular hemorrhage) and long-term sequelae (cerebral palsy [CP], diagnosed at age 6 years) were significantly associated with a below-normal non-verbal K-ABC score. Maternal fever at birth was present in five cases (11%) and eight controls (3%; odds ratio 3.6, 95% confidence interval 1.1 to 11.4). Clinical chorioamnionitis and preterm labor and/or premature rupture of membranes (as opposed to toxemia and other initiators of preterm delivery) were also more common among cases than control participants. When adjusting for potential confounders such as gestational age, maternal education and nationality, and CP, the risk estimate for maternal fever remained unchanged (3.8, 0.97 to 14.6). We conclude that perinatal infection might indeed contribute to an increased risk for long-term cognitive deficits in preterm infants.

Child↗
PubMed2003

Antenatal mycoplasma infection, the fetal inflammatory response and cerebral white matter damage in very-low-birthweight infants.

We address the question as to whether Ureaplasma urealyticum or Mycoplasma hominis, cultured from the placenta of very-low-birthweight (VLBW) infants, are associated with an increased risk of (a) fetal vasculitis and (b) ultrasonographic cerebral white matter echolucency. The sample consisted of 464 VLBW infants for whom (i) the surface of the chorion was cultured for U. urealyticum and M. hominis; (ii) the placenta was examined histologically; and (iii) a cranial ultrasound scan was obtained close to days 1, 7 or 21. Infants with echolucency were compared with controls in univariable and stratified analyses and in multivariable logistic regressions. Fifty-three per cent of placentas from infants with fetal vasculitis harboured U. urealyticum compared with 18% of controls (P </= 0.001). M. hominis was present in 14% of cases of fetal vasculitis and in 2% of controls (P </= 0.001). Among cases of echolucency, 22% had U. urealyticum compared with 30% of controls (P = 0.33), whereas 17% of these cases and 5% of controls had M. hominis (P = 0.08). Our findings support the hypothesis that U. urealyticum in the placenta of VLBW infants contributes to the fetal inflammatory response without contributing to white matter damage. Our finding that M. hominis in the placenta was associated with a not quite significant threefold risk increase for echolucency deserves further investigation.

Brain↗
PubMed2002

Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitations in children born preterm.

Only sparse information is available about a possible association between antenatal infection outside the brain and subsequent cognitive limitations among preterm infants. Based on published studies, we provide a theoretical schema that links them via the fetal inflammatory response and neonatal white matter damage. We conclude that the relationship between antenatal infection and cognitive limitations deserves much further attention by researchers interested in the prevention of this undesirable outcome of prematurity.

Acute-Phase Reaction↗