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Biomedical subjects

Olaf Dammann

Publications and source records attributed to Olaf Dammann.

At least 19 recordsLinked to original sources
PubMed2006

Incidence and clinical presentation of invasive neonatal group B streptococcal infections in Germany.

OBJECTIVE: Streptococcus agalactiae (group B Streptococcus) is an important cause of morbidity and mortality in newborn infants. So far, there have been no published data on the incidence, morbidity, and mortality of invasive neonatal group B Streptococcus infections in Germany. METHODS: A prospective active surveillance study involving all of the pediatric hospitals, which reported their cases to the German Pediatric Surveillance Unit, and all of the microbiological laboratories serving pediatric hospitals, which reported their cases to the Laboratory Sentinel Group at Robert Koch Institute Berlin, was conducted between 2001 and 2003. Capture-recapture analysis was used to evaluate the completeness of reported neonatal invasive group B Streptococcus infections. RESULTS: We collected and analyzed data from 347 and 360 infants with invasive group B Streptococcus infection during the first 3 months of life, as reported by pediatricians to the German Pediatric Surveillance Unit and microbiologists to the Robert Koch Institute Berlin, respectively. Using capture-recapture analysis, we calculated an incidence of 0.47 per 1000 live births. Nearly 60% of the infants suffered from early-onset disease, and 16% of these presented with meningitis. In contrast, 61.8% of infants with late-onset disease presented with meningitis. Prematurity was present in 22.4% of early-onset disease and 39.7% of late-onset disease cases, respectively. A high proportion of infants suffered from sequelae because of group B Streptococcus infection at the time of discharge from the hospital. Most common sequelae were hydrocephalus and cerebral seizure. Case fatality rate was 4.3%. CONCLUSIONS: This study, which is the first to provide information on the current national incidence and morbidity of invasive group B Streptococcus infection in Germany, demonstrates remarkable country-specific variation in comparison with other European countries, which gather data in a similar fashion. Therefore, the importance of country-specific prevention guidelines has to be stressed.

Germany↗
PubMed2006

Inflammation, brain damage and visual dysfunction in preterm infants.

Antenatal intrauterine infection and the fetal inflammatory response appear to be important pathogenetic factors in preterm birth and subsequent neonatal disorders of the lung and brain. In this paper, we expand this concept to include visual dysfunction. Although present data tend to support our notion, we suggest that more experimental and epidemiological research is needed to elucidate mechanisms of infection/inflammation-induced damage to the eye and visual brain pathways of preterm infants.

Brain Injuries↗
PubMed2006

Absence of pestivirus antigen in brains with white matter damage.

We previously suggested that antenatal pestivirus infection might play a role in the pathogenesis of perinatal brain white matter damage (WMD) in preterm infants. We have now examined 22 brains from stillborns and deceased newborns (both preterm and term) for the presence of bovine virus diarrhoea virus (BVDV) antigen. The brains of five females and five males with WMD (median gestational age 36.5wks), and nine female and three male controls (median gestational age 36.5wks) were used in the study. No BVDV antigen was detected in any of the 22 brains. We conclude that brain infection with BVDV is unlikely to play a role in WMD pathogenesis among preterm or term newborns. Further research is needed to test the hypothesis that intrauterine exposure to pestivirus antigen elicits a fetal inflammatory response which then contributes to WMD.

Animals↗
PubMed2006

Hospital volume and neonatal mortality among very low birth weight infants.

BACKGROUND: Very low birth weight infants (< 1500 g) are at increased mortality risk. Data on the impact of NICU volume are sparse, in comparison with those on the level of care. We hypothesized that neonatal mortality would be higher in small NICUs (< 36 very low birth weight admissions per year) than in large NICUs, with adjustment for volume of the delivery unit. METHODS: We analyzed population-based data from a quality assurance program in Lower Saxony (Germany). Perinatal data for almost all very low birth weight infants born in 1991 to 1999 (n = 7745) were available. Analyses were restricted to infants born at 24 to 30 weeks (n = 4379). Data validation procedures, univariate data analyses, and logistic regression models based on general estimating equations were performed. RESULTS: Neonatal mortality among infants admitted to NICUs was 12.2% in small NICUs and 10.2% in large NICUs. The mortality rate in small NICUs was increased significantly. Compared with infants from large delivery hospitals (> 1000 births per year) and large NICUs, the adjusted odds ratio was 1.94 for neonates for whom both units were small, 1.75 for those from large delivery units but small neonatal units, and 1.16 for those for whom only the NICU was large. Stratification according to gestational age revealed the greatest impact on mortality for infants of < 29 weeks. CONCLUSIONS: Results suggest that creating larger perinatal centers may improve perinatal health care. The volume of the NICU was associated more strongly with 28-day mortality than was the volume of the delivery hospital, and it had the largest impact on survival for infants of < 29 weeks.

Female↗
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↗