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Biomedical subjects

N Paneth

Publications and source records attributed to N Paneth.

At least 37 records · Page 2Linked to original sources

Phenobarbital compared with phenytoin for the treatment of neonatal seizures.

BACKGROUND: Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly. METHODS: From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria. RESULTS: Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment. CONCLUSIONS: Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.

Anticonvulsants↗

Sport-caught fish consumption and conception delay in licensed Michigan anglers.

Between 1993 and 1995, we surveyed 4931 licensed anglers aged 17-34 years residing in 10 Michigan counties bordering a Great Lake. Responses were received from 1443 anglers and 844 of their partners. Lifetime sport-caught fish consumption was estimated as the number of sport-caught fish meals consumed in the previous 12 months times years since 1970 in which sport-caught fish were consumed. Analysis was restricted to currently married couples (n=626). Lifetime sport-caught fish consumption was categorized in men as 0 (14%); 1-114 (27%); 115-270 (30%); 271-1127 (29%) meals; and in women as 0 (28%); 1-54 (26%); 55-138 (27%); fand 139-1127 (19%) meals, respectively. Conception delay (ever having failed to conceive after 12 months of trying) was reported by 13% of both men and women. Among men, the unadjusted odds ratios (OR) for conception delay were 1.2, 1.3, and 2.0 across the three increasing levels of sport-caught fish consumption compared to none (trend test P=0.06). After adjustment for age, race, region of Michigan, household income, educational attainment, smoking, alcohol consumption, and partner's sport fish consumption, the OR for conception delay in men were 1.4, 1.8, and 2.8, respectively. In women, unadjusted OR for conception delay were 0.9, 1.0, and 1.4 with increasing sport-caught fish consumption (trend test P=0.35). With the same covariates and the sport-caught fish consumption of the woman's partner included in the model, the OR were 0.8, 0.8, and 1.0, respectively. These data suggest a modest association, in men only, of sport-caught fish consumption with risk of conception delay.

Adolescent↗

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↗

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↗

Relation of cranial ultrasound abnormalities in low-birthweight infants to motor or cognitive performance at ages 2, 6, and 9 years.

This study sought to determine whether neonatal cranial ultrasound abnormalities are related to motor and cognitive outcomes in low-birthweight (LBW, <2000 g) children without major motor or cognitive disability. The relation of neonatal cranial ultrasound abnormalities to motor performance and general cognitive ability at ages 2, 6, and 9 years was examined in a prospectively followed regional cohort of LBW children, excluding those with major disability, and controlling for other risk factors. Compared with children without ultrasound abnormalities, children with abnormalities indicative of ischemic white-matter injury had poorer motor performance at all three ages and, at age 2, lower general cognitive ability. The latter finding was not seen when motor performance was also controlled for. It was concluded that in LBW children without major motor or cognitive disability, ischemic white-matter injury indicated by neonatal cranial ultrasound abnormalities adversely affected motor performance at ages 2, 6, and 9 years, but not general cognitive ability.

Age Factors↗

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↗

A quantitative review of mortality and developmental disability in extremely premature newborns.

OBJECTIVES: To summarize the literature on mortality rates and prevalences of major neurodevelopmental disabilities and to examine trends of these outcomes over time in extremely premature neonates. DATA SOURCES: MEDLINE was used to search the English literature for studies published since 1970 reporting on both mortality and disability in infants born at or before 26 weeks' gestation (extremely immature [EI] cohort), with a birth weight of 800 g or less (extremely small [ES] cohort), or subgroups of these. STUDY SELECTION: Studies were included in the analysis if all of the following were reported: mortality; direct examination of 75% or more of the survivors; and the proportion of patients with at least 1 of the following disabilities: cerebral palsy, mental retardation, blindness, and deafness. Studies reporting cohorts included as a subset of cohorts in another study were excluded. Forty-two studies providing mortality and disability data for 20 cohorts of 4116 EI infants and 38 cohorts of 4345 ES infants born after 1972 met the inclusion criteria. DATA EXTRACTION: Data were abstracted from all studies that met these criteria by two of us (J.M.L. and D.E.W.), independently; the data were then cross-checked to ensure accuracy. RESULTS: Survival averaged 41% for EI infants and 30% for ES infants, and it increased significantly with time. In contrast to mortality, the prevalences of major neurodevelopmental disabilities among survivors have not changed over time. The most common major disability was mental retardation, found in 14% of EI and ES survivors. Cerebral palsy was found in 12% of EI survivors and 8% of ES survivors, blindness was found in 8% of EI and ES survivors, and deafness was found in 3% of EI and ES survivors. Overall, 22% of EI survivors and 24% of ES survivors were classified as having at least 1 major disability. Each 100 EI or ES livebirths yielded 7 children with major disabilities; this prevalence was correlated with survival across cohorts. CONCLUSIONS: The prevalence of disabilities had not changed among EI or ES survivors with increasing survival. However, increasing survival of these infants has resulted in a steadily increasing prevalence of children with disabilities.

Birth Weight↗

Groups of histopathologic abnormalities in brains of very low birthweight infants.

The neuropathologic changes in brains of very premature infants are well recognized but relatively few studies have attempted to identify if specific neuropathologic features cluster together. These data could assist in determining pathogenetic mechanisms of immature brain injury. The goal of this study is to identify which, if any, combinations of histologic features occur together. We identified the presence or absence of 19 histologic features in the brains of 67 infants from a multicenter study of 1,665 prematurely born infants whose birthweight was 500-1,500 grams. We used clustering algorithms and factor analysis to group pathologic features that occurred together. Our results indicate that certain histopathologic features do cluster. For example, telencephalic white matter astrocytosis occurs in 2 groups: 1) associated with amphophilic globules, and, 2) in an uncorrelated group, associated with focal macrophage deposits and coagulative necroses. Parenchymal hemorrhage was not found to be associated with any telencephalic leukoencephalopathy, regardless of whether characterized by rarefaction, astrocytosis, focal coagulative necroses, or foci of macrophages in the white matter. Intraventricular hemorrhage and germinal matrix hemorrhage were not seen together more often than by chance expectation. Intraventricular hemorrhage was only marginally associated with parenchymal hemorrhage. Our data indicate that specific histopathologic features tend to preferentially cluster with each other in groups. This clustering may represent the manifestation of a common mechanism for each. These data should be valuable indicators for future research attempting to establish pathogenesis.

Algorithms↗

The apgar score and its components in the preterm infant.

OBJECTIVE: The Apgar score is well-characterized in full-term infants but not in premature infants. The objective of this study was to assess the Apgar score in preterm infants with respect to the relationships between the 1- and 5-minute scores, the correlation of the Apgar score with pH and with other variables, and the relationship among the individual Apgar components. METHODOLOGY: We recorded Apgar scores at 1 and 5 minutes in a population-based cohort of preterm infants (n = 1105) with birth weight <2000 g, from three intensive care nurseries in central New Jersey. Linear correlation analysis was used to examine the relationship between 1- and 5-minute Apgar scores and between the individual components of the Apgar score. Multiple regression analysis was used to explore the relationship between various perinatal characteristics and the Apgar score, and between pH and Apgar score. Stepwise logistic regression analysis was used to assess the determinants of mortality. RESULTS: The 1-minute Apgar score median (25%, 75%) was 6(4,8) and correlated with the 5-minute score of 8(7,9) at r = .78. Slight but significant differences were seen between male (n = 557) and female (n = 508) infants in the 1-minute (6[4,8] and 7[4,8]) Apgar scores. One- and 5-minute scores of white infants (7[4,8] and 8[7,9]; n = 713) were significantly higher than those of black infants (5[3,7] and 8[6,9]; n = 280). Birth weight and gestational age were both linearly related to both Apgar scores. Low Apgar score (<3 at 1 minute and <6 at 5 minutes) was significantly associated with birth weight, gestational age and mode of delivery. Low arterial blood pH (<7.01) at birth was significantly related to low Apgar score. One hundred fifty-nine infants died; these infants were significantly smaller (983 +/- 382 vs 1462 +/- 369 g), less mature (27 vs 31 weeks), had lower arterial blood pH (7.20 +/- 0.18 vs 7.31 +/- 0.11), had lower 1- (3[2,6] vs 7[4,8]) and 5-minute Apgar scores (6[4,8] vs 8[7,9]), and a greater incidence of low Apgar score (32% vs 6%) than did survivors. CONCLUSIONS: Among the components of the Apgar score, respiratory effort, muscle tone, and reflex activity correlated well with one another; heart rate correlated less well; and color the least. Our data confirms the limited use of the Apgar score in preterm infants and demonstrates the different responses of the Apgar score's components.

Black or African American↗

A rivalry of foulness: official and unofficial investigations of the London cholera epidemic of 1854.

Contemporaneous with John Snow's famous study of the 1854 London cholera epidemic were 2 other investigations: a local study of the Broad Street outbreak and an investigation of the entire epidemic, undertaken by England's General Board of Health. More than a quarter-century prior to Koch's description of Vibrio comma, a Board of Health investigator saw microscopic "vibriones" in the rice-water stools of cholera patients that, in his later life, he concluded had been cholera bacilli. Although this finding was potential evidence for Snow's view that cholera was due to a contagious and probably live agent transmitted in the water supply, the Board of Health rejected Snow's conclusions. The Board of Health amassed a huge amount of information which it interpreted as supportive of its conclusion that the epidemic was attributable not so much to water as to air. Snow, by contrast, systematically tested his hypothesis that cholera was water-borne by exploring evidence that at first glance ran contrary to his expectations. Snow's success provides support for using a hypothetico-deductive approach in epidemiology, based on tightly focused hypotheses strongly grounded in pathophysiology.

Air Microbiology↗

Does transient hypothyroxinemia cause abnormal neurodevelopment in premature infants?

THOP is a relatively common condition whose long-term effects remain uncertain. The preponderance of evidence indicates that at the very least THOP is a marker of elevated risk of neurodevelopmental adversity, but whether this association is truly causal and whether thyroxine treatment in the neonatal period can prevent adverse outcome is as yet unknown. Since the number of infants born and surviving at very early gestations continues to increase, the importance of this condition will be magnified in the future. The major difficulty in establishing the causal role of THOP is the tangled time order of events in the early neonatal period. It is therefore unlikely that further observational studies will advance understanding. Energies should be focused on Assessing neurodevelopment objectively in survivors in each of the TRH trials. Developing a new multicenter trial of newborn supplementation with thyroid hormone that is carefully planned to have sufficient power to assess neurodevelopment in treated and untreated infants under a variety of baseline conditions.

Developmental Disabilities↗