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O Dammann

Publications and source records attributed to O Dammann.

At least 37 records · Page 2Linked to original sources
PubMed2001

Is periventricular leukomalacia an axonopathy as well as an oligopathy?

Periventricular leukomalacia is a white matter disorder, the neonatal cranial ultrasound images of which predict long-term developmental limitations among preterm infants. The vulnerability of oligodendrocytes has led to the hypothesis that oligodendrocytes suffer the primary damage, with axonal damage occurring as a consequence. In this article, we discuss the differential role of oligodendrocytes and axons in this disorder's etiology, offering analogies from the multiple sclerosis and hydrocephalus literature. We conclude that it is too early to view periventricular leukomalacia exclusively as a consequence of oligodendrocyte damage and/or maldevelopment.

Axons↗
PubMed2001

Symptom-limited stair climbing as a predictor of postoperative cardiopulmonary complications after high-risk surgery.

STUDY OBJECTIVE: Thoracotomy, sternotomy, and upper abdominal laparotomy are associated with high rate of postoperative cardiopulmonary complications (POCs). We hypothesized that symptom-limited stair climbing predicts POCs after high-risk surgery. DESIGN: A prospective evaluation of 83 patients undergoing thoracotomy, sternotomy, and upper abdominal laparotomy surgery. METHODS: The 52 men and 31 women completed symptom-limited stair climbing. A separate investigator, blinded to the number of flights of stairs climbed, assessed 30-day actual outcomes for POCs, including pneumonia, atelectasis, mechanical ventilation for > 48 h, reintubation, myocardial infarction, congestive heart failure, arrhythmia, pulmonary embolus, and death within 30 days of surgery. The operations performed included 31 lobectomies, 6 wedge resections, 3 pneumonectomies, 3 substernal thymectomies, 1 substernal thyroidectomy, 23 colectomies, 3 laparotomies, 7 abdominal aortic aneurysm repairs, 5 esophagogastrectomies, and 1 nephrectomy. RESULTS: POCs occurred in 21 of 83 patients (25%) overall, in 9 of 44 patients undergoing thoracotomy/sternotomy (20%), and in 12 of 39 patients undergoing upper abdominal laparotomy (31%). Of those unable to climb one flight of stairs, 89% developed a POC. No patient able to climb the maximum of seven flights of stairs had a POC. The inability to climb two flights of stairs was associated with a positive predictive value of 82% for the development of a POC. The number of days in the hospital postoperatively decreased with a patient's increased ability to climb stairs. CONCLUSIONS: Symptom-limited stair climbing offers a simple, inexpensive means to predict POCs after high-risk surgery.

Abdomen↗
PubMed2000

Brain damage in preterm newborns: biological response modification as a strategy to reduce disabilities.

Substances that promote the growth and maturation of oligodendrocytes and their precursors might protect against white matter injury. We suggest that neuroprotection can also be provided by such modulators of fetal and neonatal inflammatory responses as antiinflammatory cytokines, cytokine-binding proteins, and cytokine-receptor blockers. We briefly describe inflammatory responses in the fetus and newborn and show how they might contribute to brain damage. We conclude with the possibility that so-called biological response modifiers, which are drugs that modulate these inflammatory responses, might reduce the risk of brain damage and disabilities.

Brain Damage, Chronic↗
PubMed2000

Antecedents of cerebral palsy in very low-birth weight infants.

Research from the last two decades provides directions for efforts to prevent CP in VLBW infants. The pathogenesis of CP seems to involve factors operating both during pregnancy and in the neonatal period. The most important prenatal factor appears to be intrauterine infection. Perinatal infection and other risk factors, such as the death of a co-twin, placental abruption, and cerebral ischemia, could trigger a cytokine cascade resulting in damage to the developing brain. The low frequency of intrauterine infection in mothers with preeclampsia might explain the apparent protective effect of this disorder. If the brain damage attributed to intrauterine infection and other risk factors involves cytokines as intermediates, then blockade of the proinflammatory cascade or promotion of endogenous inhibitors might prevent CP. Other potentially preventive strategies include corticosteroids given to mothers (but not those given to neonates) and thyroid hormone.

Abruptio Placentae↗
PubMed2000

What explains away the increased risk of histological chorioamnionitis in African-American mothers of very-low-birthweight infants? Developmental Epidemiology Network Investigators.

We sought explanations for African-American mothers' increased risk of chorioamnionitis by sequentially adjusting for confounder variables both individually and in groups. We searched for a subset of covariates that had the most influence on the chorioamnionitis odds ratio (OR) of these women. The sample consisted of 305 African-American and 520 White mothers who gave birth to a very-low-birthweight (< or = 1500 g) infant between 1991 and 1993, whose placenta was examined according to protocol and whose hospital chart was reviewed. Histologically proven chorioamnionitis was present in 43% of the placentas from African-American women and in 27% of those from Whites (crude OR 2.1, 95% confidence interval 1.5, 2.8). Singleton status appeared to be the most important effect modifier, with significant crude ORs of 1.5 among singletons and 3.4 among non-singletons. Using logistic regression models in the whole sample and in subgroups, we sought to 'explain away' this increased risk. Indeed, addition of information about confounder variables resulted in considerable reduction in the ORs to 1.1 among singletons and 1.9 among non-singletons. Particularly important among the confounders were singleton birth, Medicaid insurance, duration of ruptured membranes and gestational age. We discuss the possibility that this set of confounding variables conveys, in part, the same information as the variable African-American, and also perhaps information about the availability and/or utilisation of prenatal health care.

Black or African American↗
PubMed2000

New research directions in neuroepidemiology.

Many of the risk factors previously identified for disorders such as Alzheimer's disease, periventricular leukomalacia, multiple sclerosis, stroke, cerebral palsy, mental retardation, and acquired learning and attention disorders ultimately may be shown to damage the central and peripheral nervous systems through activation of inflammatory mediators. The challenge to epidemiologists in the future is to expand use of epidemiologic methods to explore how immune-mediated insults produce CNS disorders in human populations. Studies of the association of use of nonsteroidal anti-inflammatory drugs with risk of Alzheimer's disease and those of the association of immune parameters with risk of cerebral palsy are excellent examples of how epidemiology can contribute to our understanding of the causes of neurologic and/or neurodevelopmental disorders. Many of the immune parameters of interest have short half-lives and are difficult to measure outside of the laboratory setting. Questions also remain as to the proper timing of measurements in relation to the initial insult and, in some cases, which tissue is the most appropriate to sample. These measurement issues will need to be resolved before use of immune biomarkers in epidemiologic studies of the etiologies of neurologic disorders can be fully realized. Epidemiologists are most likely to help identify ways to prevent neurologic disorders if they are knowledgeable about the molecular biology of inflammation, modulators of CNS vulnerability, and genetic polymorphisms that influence both inflammation and CNS vulnerability and are prepared to become adept at biomarker epidemiology. This does not necessarily compel them to gain extensive knowledge of neurobiology. Rather, neuroepidemiology in the 21st century will require increased collaboration between epidemiologists, neurologists, and neurobiologists.

Aged↗
PubMed2000

Role of the fetus in perinatal infection and neonatal brain damage.

Increasing evidence supports the view that infants exposed to perinatal infection are at increased risk for brain injury. We suggest that elevated cytokines in the amniotic fluid or in the fetal circulation be viewed as a humoral expression and that inflammatory cells in chorionic plate or umbilical cord blood vessel walls be viewed as a morphologic expression of the fetal inflammatory response. We discuss the evidence supporting the hypothesis that the fetal inflammatory response contributes to neonatal brain injury and later developmental disability. Little support has been found for a maternal contribution. Intervention should be designed with the fetus in mind.

Amniotic Fluid↗
PubMed1999

Antenatal corticosteroids and cranial ultrasonographic abnormalities.

OBJECTIVE: This study was undertaken to determine whether very-low-birth-weight infants whose mothers received a course of antenatal corticosteroids were at decreased risk for 3 cranial ultrasonographic entities that predict neurodevelopmental dysfunction. STUDY DESIGN: This retrospective cohort study evaluated 1604 infants weighing 500 to 1500 g who underwent >/=1 of 3 cranial ultrasonographic scans required by design at specified postnatal intervals and whose own and mother's hospital charts were reviewed. Infants were classified according to mother's course of antenatal corticosteroids (none, partial, or complete). RESULTS: In the total sample the risks of intraventricular hemorrhage and of an echolucent image in the cerebral white matter were only modestly (and not statistically significantly) reduced after a full course of antenatal corticosteroids, whereas antenatal corticosteroids appeared to significantly reduce the risk of ventriculomegaly after even a partial course. Antenatal corticosteroids appeared to halve the risk of ventriculomegaly and echolucent image among the gestationally youngest infants and those with intraventricular hemorrhage, hypothyroxinemia, or vasculitis of the umbilical cord or chorionic plate of the placenta. CONCLUSION: These observations are consistent with the hypothesis that antenatal corticosteroids protect very-low-birth-weight infants, especially those who are most vulnerable, against the risk of cranial ultrasonographic abnormalities.

Adrenal Cortex Hormones↗
PubMed1999

White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. The Developmental Epidemiology Network.

OBJECTIVES: Because intraventricular hemorrhage (IVH) often precedes the development of sonographically defined white matter damage (WMD) in very preterm infants, we sought to identify the IVH characteristics that predict WMD. HYPOTHESES: We evaluated variations on the null hypothesis that infants with IVH are no more likely than infants without IVH to have WMD. These variations dealt with characteristics of the IVH (presence or absence of ventriculomegaly) or characteristics of the WMD (size, localization, and laterality). METHODS: A total of 1605 infants weighing 500 to 1500 g at birth between January 1991 and December 1993 underwent standardized cranial ultrasound studies with 6 standard coronal and 5 sagittal views at postnatal days 1 to 3, 7 to 10, and at 3 to 8 weeks. RESULTS: A total of 129 (8%) infants had WMD, either an echodensity alone (n = 59), an echolucency alone (n = 18), or both (n = 52). In analyses that controlled for gestational age, IVH was associated with a fivefold to ninefold increased risk of WMD regardless of size, laterality, or extent of lesions (P </=.0005). Compared with infants with neither IVH nor ventriculomegaly, infants with both were at 18- to 29-fold greater risk of WMD (P </=.0005). CONCLUSIONS: In this study IVH and ventriculomegaly were powerful predictors of WMD occurrence, whether small or large, unilateral or bilateral, localized or diffuse.

Brain Diseases↗
PubMed1999

Hypothyroxinemia of prematurity and the risk of cerebral white matter damage.

OBJECTIVE: Infants with hypothyroxinemia of prematurity (HOP) are at increased risk for neurodevelopmental dysfunction. Infants born near the end of the middle trimester are also at increased risk for an echolucency (EL) in the cerebral white matter, which reflects white matter damage and is the cranial ultrasound abnormality that best predicts neurodevelopmental dysfunction. We postulated that some of the increased risk of neurodevelopmental problems associated with HOP reflects an increased risk of EL. STUDY DESIGN: We studied 1414 infants weighing 500 to 1500 g who were born at 4 medical centers between 1991 and 1993. The infants had thyroxine blood levels measured during the first weeks of life, at least 1 of 3 cranial ultrasound scans performed at specified postnatal intervals, and their own and their mother's hospital charts reviewed. Infants were classified by whether or not their first thyroxine level placed them in the lowest quartile among all infants in this sample (ie, <67.8 nmol/L, our definition of HOP, equivalent to <5.3 micrograms/dL). RESULTS: After adjusting for such potential confounders as low gestational age and measures of illness severity, infants with HOP had twice the risk of EL as their peers with higher thyroxine levels. CONCLUSION: Our findings are consistent with the hypothesis that a "normal" blood thyroxine level protects infants born near the end of the middle trimester against the risk of cerebral white matter damage.

Brain↗
PubMed1999

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators.

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

Brain Damage, Chronic↗
PubMed1999

Brain damage in preterm newborns: might enhancement of developmentally regulated endogenous protection open a door for prevention?

We present a two-component model of brain white matter damage in preterm neonates. The insult component comprises infection and hypoxia-ischemia, which are both associated with inflammation-related abnormalities in the white matter. The developmental component comprises at least three factors, ie, immaturity of the ependymal/endothelial, oligodendroglial, and endogenous protection systems. All three factors are likely contributors to an increased vulnerability of the preterm newborn's white matter. In this article, we focus on recent developments in oligodendrocyte biology that support the view of certain cytokines and growth factors as oligotrophins based on their capability to enhance oligodendrocyte development or survival. We suggest that research into networks of developmentally regulated endogenous protectors (such as oligotrophins) is necessary to broaden our perspectives in brain injury prevention in preterm newborns.

Brain Damage, Chronic↗
PubMed1998

Increased risk of spastic diplegia among very low birth weight children after preterm labor or prelabor rupture of membranes.

Our objective was to study the association of spastic diplegia (SDP; N = 29) with the initiator of preterm birth in a regional cohort of 312 6-year-old very low birth weight children (< or =1500 gm). We determined the prevalence of SDP among those children born after idiopathic preterm onset of labor (POOL) or prelabor rupture of membranes (PROM) (12% SDP), and among those born after pregnancy-induced hypertension or other medical indications for preterm delivery (4% SDP). Stratification showed that 83% of the children with diplegia were born after POOL or PROM. The threefold increased risk of SDP among those children born after POOL or PROM compared with the remainder of the cohort (crude odds ratio 3.2, 95% confidence interval 1.2 to 8.5) remained elevated after controlling for perinatal and neonatal variables (odds ratio 2.4 to 2.7) in logistic regression models. We conclude that birth after POOL or PROM increases the risk of SDP among very low birth weight children and speculate that this might be related to infectious processes leading to both POOL or PROM and SDP.

Cerebral Palsy↗
PubMed1998

Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant.

This review synthesizes the literature supporting the hypothesis that infection during or even before pregnancy remote from the fetal brain leads to neonatal white matter damage (NWMD) and its long-term sequelae, including cerebral palsy. First, a framework of five dimensions is presented, including the spectrum of NWMD, its relationship with gestational age, its clinical spectrum, the expressions and correlates of infection, and the mother/child dyad. Second, a summary of the plethora of support for the remote infection/NWMD-hypothesis is presented by drawing on studies published over the past three decades. Although an epidemiological perspective is prominent, we invoke molecular explanations (especially the cytokine hypothesis) for observed associations. Third, the article concludes with a section on future studies needed to characterize and eliminate (pre-) pregnancy infections in the mother and to identify and evaluate potentially neuroprotective strategies in the fetus.

Brain Injuries↗