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Biomedical subjects

A Leviton

Publications and source records attributed to A Leviton.

At least 19 recordsLinked to original sources
PubMed2004

Fetal vasculitis in preterm newborns: interrelationships, modifiers, and antecedents.

Histologic expressions of the fetal inflammatory response predict preterm delivery and neonatal disorders. We examined 1146 placentas in the Developmental Epidemiology Network data set for histologic evidence of membrane inflammation (subchorionitis, chorionitis, and chorioamnionitis) and fetal vasculitis (acute umbilical vasculitis or chorionic vasculitis). Our main findings are that (1) in the presence of membrane inflammation, fetal vasculitis is common, (2) duration of membrane rupture and gestational age appear to modify the risk of fetal vasculitis, (3) this risk modification differs for the different components of fetal vasculitis, i.e. umbilical and chorionic vasculitis, and (4) antecedents can be identified that appear to increase or decrease the risk of fetal vasculitis among births with membrane inflammation. We conclude that fetal vasculitis, the morphologic component of the fetal inflammatory response, might not be a homogeneous entity and deserves further study.

Adult↗
PubMed2002

A review of the literature relating caffeine consumption by women to their risk of reproductive hazards.

From this detailed review of the literature, several conclusions can be drawn: (a) An association between caffeine consumption and a reproductive hazard is more likely to be seen in lower-quality studies than in studies that come closer to approximating the ideal. This is especially evident for "lower" birthweight and congenital anomalies. (b) The association between caffeine consumption and spontaneous abortion may well reflect the Stein-Susser epiphenomenon (women with prominent nausea tend to reduce caffeine consumption and nausea appears to be a marker of good implantation, perhaps reflecting a favorable balance of hormones produced by a healthy placenta). (c) The claim that caffeine consumption by women delays conception has not been followed by convincing support. (d) Reproductive hazards associated with cigarette smoking tend to be associated with caffeine/coffee consumption. Sometimes this appears to be a consequence of residual confounding associated with inadequate adjustment for cigarette smoking, which is over-represented among those who drink the most coffee/caffeine. Sometimes this reflects the tendency of women to underreport socially undesirable behaviors (e.g. smoking) while accurately reporting socially neutral behaviors (e.g. coffee and caffeine consumption). Thus, it seems reasonable to conclude that no convincing evidence has been presented to show that caffeine consumption increases the risk of any reproductive adversity.

Abnormalities, Drug-Induced↗
PubMed2002

Adult stroke and perinatal brain damage: like grandparent, like grandchild?

Biomarkers of inflammation are found in the circulation of adults who have had a stroke. Although these biomarkers may, in part, be indicators of damage, some appear to contribute to damage. Similar biomarkers are found in newborns with cerebral white matter damage or at risk of cerebral palsy. Can we learn about the pathogenesis of neonatal white matter damage from what has been learned about the inflammatory correlates of adult stroke? We discuss relevant findings about systemic inflammatory markers in adult stroke and relate this information to our current understanding of cerebral white matter damage in newborns, especially those born at an extremely low gestational age. We also describe desirable characteristics of future studies of perinatal brain damage that involve measurements of systemic biomarkers.

Adult↗
PubMed2002

Brain damage markers in children. Neurobiological and clinical aspects.

UNLABELLED: The presence in blood of proteins normally confined to the cytoplasm of brain cells is considered peripheral evidence of brain damage. Only recently have these proteins been measured in the blood of children at risk of brain damage. To show the value and limitations of measuring these proteins, we review their biology and the adult literature that has correlated the blood concentrations of these proteins with lesion size and dysfunction. CONCLUSION: We conclude that brain damage markers will increasingly be measured in the blood of newborns and other children at risk of brain damage.

Biomarkers↗
PubMed2001

Mediators of fetal inflammation in extremely low gestational age newborns.

To establish levels of mediators of inflammation in cord blood and postnatal serum from extremely low gestational age newborns (ELGANs, < or =28 weeks), we measured sixteen markers of inflammation by recycling immunoaffinity chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of IL-1, IL-6, IL-8, IL-11, IL-13, TNF-alpha, G-CSF, M-CSF, GM-CSF, MIP-1alpha, and RANTES were considerably higher than published values of these inflammatory mediators from term newborns. In three of eight ELGANS who had serial measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-alpha, G-CSF, and MIP-1alpha declined from initially very high levels to reach an apparent baseline towards the end of the first postnatal week. In these same three infants, GM-CSF and TGF-beta1 levels increased continuously during the first week. In the other five ELGANs, no consistent changes were observed. We speculate, that in some ELGANs, a fetal systemic inflammatory response is characterized by an antenatal wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti-inflammatory cytokines. Large epidemiologic studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of inflammatory mediators in the pathophysiology of the major complications of extreme prematurity.

Adult↗
PubMed2001

Do white cells matter in white matter damage?

Support is provided for the hypothesis that activated leukocytes, especially monocytes/macrophages, contribute to cerebral white matter damage in extremely low gestational age newborns. Much of the evidence is indirect and comes from analogies to brain diseases in adults, and from models of brain damage in adult and newborn animals. If the recruitment of circulating cells to the brain contributes to white matter damage in extremely low gestational age newborns, then minimizing the transendothelial migration of circulating cells by pharmacological manipulation might prevent or reduce the occurrence of neonatal white matter damage and the disabilities that follow.

Animals↗
PubMed2001

Growth-restricted premature infants are at increased risk for low thyroxine.

OBJECTIVE: To evaluate, in extremely premature infants, the relationship between growth restriction and early total thyroxine levels, and to determine how maternal, prenatal, perinatal and neonatal variables influence the relationship. STUDY DESIGN: 719 infants born at four medical centers in Massachusetts, New York and New Jersey between 1991 and 1993 were studied. Entry criteria included: gestational age 23--30 weeks, birth weight 500--1500 g, and a serum thyroxine level obtained in the first week of life. Infants born to mothers with a history of thyroid disease were excluded. Birth weight and total thyroxine level are expressed as z-scores (standard deviation units) to adjust for their relationship to gestational age. RESULTS: In linear regression analysis, there was a 0.18 decrease in the total thyroxine z-score for each 1.0 (1 standard deviation unit) decrease in birth weight z-score (p=0.0001). Adjustment for multiple potential maternal, prenatal, perinatal and neonatal confounders failed to identify a factor or factors that could account for the observed association. CONCLUSIONS: The early total thyroxine level in extremely preterm infants was significantly associated with birth weight z-score. This relationship persisted even after adjustment for maternal, prenatal, perinatal and neonatal confounders suggesting antenatal influences. Of clinical importance, growth-restricted infants are at increased risk for early hypothyroxinemia and, possibly, to its related morbidities.

Adult↗
PubMed2001

Antenatal glucocorticoid treatment does not reduce chronic lung disease among surviving preterm infants.

BACKGROUND: Antenatal glucocorticoid treatment (AGT) is associated with a number of postnatal benefits to the preterm infant, including reduced risk of respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. OBJECTIVE: To evaluate the hypothesis that maternal AGT not only reduces the risk of surfactant deficiency but also reduces the occurrence of chronic lung disease (CLD) among surviving preterm infants. STUDY DESIGN: Case-referent study of 1454 very low birth weight infants born between January 1991 and December 1993 at 4 university medical centers. RESULTS: Rates of AGT varied among the 4 centers (11%-69%), as did rates of CLD (4%-21%), defined as a requirement for supplemental oxygen at 36 weeks' postmenstrual age. CLD rates at each center, however, did not vary with the rate of AGT exposure. In multivariate logistic regression analyses, AGT did not contribute significantly to CLD risk. CONCLUSION: AGT may play a less prominent role in modifying CLD risk than other factors such as biologic immaturity, infection, or neonatal intensive care unit practices, such as mechanical ventilation, continuous positive airway pressure, and surfactant replacement therapy.

Chronic Disease↗
PubMed2001

Congenital microcephaly: phenotypic features in a consecutive sample of newborn infants.

OBJECTIVE: We compared the prevalence of major and minor anomalies in a consecutive sample of newborn infants with congenital microcephaly with that among normocephalic infants. STUDY DESIGN: Head measurements from >19,000 liveborn infants at 1 hospital during the years 1991 and 1992 were reviewed. Infants whose head circumference was in the lowest quartile (n = 850) were remeasured by research assistants to identify all whose head circumference was 2 SD below the mean for gestational age; 106 infants with congenital microcephaly were identified. Infants with microcephaly (n = 65) and 294 infants in a control group were examined systematically for major malformations and minor physical features. RESULTS: Four (6.2%) of the 65 infants examined either had a major malformation or were considered dysmorphic. One of the 4 had a specific multiple malformation syndrome, and 1 dysmorphic infant had a rare metabolic defect. Overall, the infants with microcephaly did not have a higher frequency of minor anomalies. However, there was a higher frequency of frontal bossing, small chin, and short nose with anteverted nares, which was associated with small body size rather than microcephaly. CONCLUSIONS: Congenital microcephaly is infrequently accompanied by major malformations and occurs rarely as part of a recognizable syndrome.

Abnormalities, Multiple↗
PubMed2001

Possible strategies to protect the preterm brain against the fetal inflammatory response.

The accruing evidence that a fetal inflammatory response is the link between antenatal infection and white matter damage in the preterm newborn infant offers room for speculation how this harmful sequence could be interrupted. Enhancement of endogenous protection, response modification, and damage limitation downstream could be helpful strategies for intervention design. Appropriate observational and experimental studies are needed before clinical interventions can be initiated.

Antibodies↗
PubMed2001

Topography of cerebral white-matter disease of prematurity studied prospectively in 1607 very-low-birthweight infants.

The objective of this study was to evaluate to what extent (1) the characteristics of localization, distribution, and size of echodense and echolucent abnormalities enable individuals to be designated as having either periventricular hemorrhagic infarction or periventricular leukomalacia and (2) the characteristics of periventricular hemorrhagic infarction and periventricular leukomalacia are independent occurrences. The population for this study consisted of 1607 infants with birthweights of 500 to 1500 g, born between January 1991 and December 1993, who had at least one cranial ultrasound scan read independently by at least two ultrasonographers. The ultrasound data collection form diagrammed six standard coronal views. The cerebrum was divided into 17 zones in each hemisphere. All abnormalities were described as being echodense or echolucent and were classified on the basis of their size, laterality, location, and evolution. Eight percent (134/1607) of infants had at least one white-matter abnormality. The prevalence of white-matter disease decreased with increasing gestational age. Most abnormalities were small or medium sized and unilateral; only large echodensities tended to be bilateral and asymmetric. Large abnormalities, whether echodense or echolucent, were more likely than smaller abnormalities to be widespread, and the extent of cerebral involvement was independent of whether abnormalities were unilateral or bilateral. Large abnormalities were relatively more likely than small abnormalities to involve anterior planes. Small abnormalities, whether echodense or echolucent, or whether unilateral or bilateral, preferentially occurred near the trigone. Using the characteristics of location, size, and laterality/symmetry, we were able to allocate only 53% of infants with white-matter abnormalities to periventricular hemorrhagic infarction or periventricular leukomalacia. Assuming that periventricular leukomalacia and periventricular hemorrhagic infarction are independent and do not share risk factors, and that each occurs in approximately 5% of infants, we would have expected 0.25%, or about 4 individuals, to have abnormalities with characteristics of both periventricular leukomalacia and periventricular hemorrhagic infarction, whereas we found 63 such infants. Most infants with white-matter disease could not be clearly designated as having periventricular hemorrhagic infarction or periventricular leukomalacia only. Periventricular hemorrhagic infarction contributes to the risk of periventricular leukomalacia occurrence, or the two sorts of abnormalities share common risk antecedent factors. The descriptive term echodense or echolucent and the generic term white-matter disease of prematurity should be used instead of periventricular leukomalacia or periventricular hemorrhagic infarction when referring to sonographically defined white-matter abnormalities.

Brain Mapping↗
PubMed2001

Hypocarbia during the first 24 postnatal hours and white matter echolucencies in newborns < or = 28 weeks gestation.

The purpose of the present study was to test the hypothesis that newborns < or = 28 wk gestation who have a PCO(2) measurement in the lowest gestational age-specific quartile (hypocarbia) on the first day of life are not at increased risk for ultrasonographic white matter echolucency (EL) after adjustment for confounders. The sample consisted of 799 infants < or = 28 wk gestation born during 1991-1993. Forty-eight infants with EL were classified as cases and compared with 751 controls, i.e. those without EL. We performed univariable comparisons, stratified analyses, and multivariable logistic regression. In the univariable analyses, hypocarbia on the first day of life was associated with an increased EL risk. The odds ratios for the hypocarbia-EL relationship were prominently elevated in the strata of infants who did not have other major risk factors for EL (e.g. gestational age 26-28 wk, normothyroxinemia, no characteristics of antenatal infection). In the multivariable analyses, the association diminished after adjustment with a hypocarbia propensity score (odds ratio = 1.7; 95 % confidence interval, 0.8-3.2) or with potential confounders.

Brain↗
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↗
PubMed2000

Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors. Children Brain Tumor Consortium.

BACKGROUND: In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. METHODS: The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors. RESULTS: Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas. When the specific combinations of the three features were unambiguously designated, three diagnostic categories resulted. These revised diagnostic categories are consistent with WHO guidelines and have significantly different survival distributions. However, neither the original WHO diagnoses nor the revised categories adequately separated these tumors prognostically, because histologic features other than those specified by WHO were significantly associated with improved or worsened survival. CONCLUSIONS: Classifications based on small numbers of specified histologic features may not be feasible because they inadequately separate childhood astrocytic tumors into prognostically homogeneous groups. Preferable classification techniques are those that simultaneously account for all reliably recognized histologic features.

Adolescent↗
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

Reduced visual resolution acuity and cerebral white matter damage in very-low-birthweight infants.

Neonatal cerebral white matter echolucencies predict visual resolution acuity deficits in very-low-birthweight (VLBW) infants. We examined maternal sociodemographic, lifestyle, intrapartum, infant birth/perinatal, and ocular motor/refractive characteristics to determine whether they accounted for this association in infants who were tested once between postnatal age 25 and 56 weeks (corrected for gestational age at birth). Cranial ultrasound scans were read by consensus to identify echolucency in a population of VLBW infants with no known ocular abnormalities. Visual resolution acuity was measured with the Acuity Card Procedure (ACP) in 14 infants with echolucency and compared with that of 81 VLBW infants born in the same hospitals with normal ultrasound scans. In time-oriented logistic regression models, echolucency remained a consistent predictor of abnormal visual resolution acuity after adjustment for covariates in three developmental periods (pre-, peri-, and postnatal). Odds ratios ranged from 19.3 (95% confidence interval, 4.5 to 82.2; p=0.001) to 10.4 (95% confidence interval, 1.3 to 81.9; p=0.03). Reduced visual resolution acuity in VLBW infants appears to be due to cerebral white matter damage.

Cerebral Cortex↗