PubMed Health⌕ Search

Biomedical subjects

L R Ment

Publications and source records attributed to L R Ment.

At least 37 records · Page 2Linked to original sources
PubMed1997

Antecedents of cerebral palsy in a multicenter trial of indomethacin for intraventricular hemorrhage.

OBJECTIVES: To determine if cerebral palsy (CP) rates were lower in the active treatment group compared with the control group, as improved survival rates of very low-birth-weight infants are postulated to be the cause of the increased incidence of CP in preterm infants, to evaluate relationships between multiple prenatal, perinatal, and postnatal variables and CP to understand better its antecedents in very low-birth-weight infants in the era of surfactant replacement therapy, and to determine the usefulness of a cranial ultrasonographic (US) scan in predicting CP. DESIGN: Inception cohort follow-up study as part of a randomized controlled trial of low-dose indomethacin sodium for the prevention of intraventricular hemorrhage. SETTING: Neonatal intensive care units at 3 medical centers. PATIENTS: Infants with birth weights between 600 and 1250 g were eligible, and 505 infants were enrolled in the original study. Of these infants, 440 (87%) survived; neurologic examinations were completed on 381 infants (86%) at 36 months corrected age. MAIN OUTCOME MEASURES: Statistical analyses were performed to identify the antecedents of CP, including the results of frequent cranial US scans obtained throughout the newborn period. RESULTS: Cerebral palsy was found in 36 (9.5%) of 381 infants at 36 months corrected age (range, 33-39 months corrected age). Univariate analysis identified chorioamnionitis, treatment with surfactant, bronchopulmonary dysplasia, and abnormal cranial US findings as antecedents of CP. Periventricular leukomalacia and ventriculomegaly were associated with the highest detection rates for CP (37% and 30%, respectively) with acceptable false-positive rates. Multivariate analysis identified bronchopulmonary dysplasia and an abnormal cranial US scan showing grade 3 to 4 intraventricular hemorrhage, periventricular leukomalacia, or ventriculomegaly as independent predictors of CP. Odds ratios for the detection of CP using cranial US findings tabulated by hospital day were in the range of 7 to 26 beginning on day 2. CONCLUSION: The results suggest that cranial US findings are useful predictors of CP during a patient's stay in the hospital.

Cerebral Hemorrhage↗
PubMed1997

An in vitro three-dimensional coculture model of cerebral microvascular angiogenesis and differentiation.

The microvasculature of the developing brain is plastic and responds differently to the many insults associated with preterm birth. We developed three-dimensional in vitro culture models for the study of the responses of the developing cerebral microvasculature. Beagle brain microvascular endothelial cells (BBMEC) were isolated by differential centrifugation from newborn beagle pups on postnatal Day 1 and placed in three-dimensional culture dispersed in a collagen gel. Alternatively, BBMEC were placed in a three-dimensional coculture with neonatal rat forebrain astrocytes. Cultures were analyzed for extracellular matrix components at 1 and 6 d, and total RNA was extracted for Northern analyses. Urokinase plasminogen activator activity was assayed in both mono- and cocultures of the two cell types. Studies of three-dimensional BBMEC/astrocyte cocultures demonstrated progressive tube formation with only low levels of endothelial proliferation. By 6 d in three-dimensional coculture, the BBMEC formed capillarylike tubes with a wrapping of glial processes, and basement membrane protein synthesis was noted. Urokinase plasminogen zymography suggested intercellular signaling by the two cell types. These data suggest that the three-dimensional beagle brain germinal matrix microvascular endothelial cell/neonatal rat astrocyte coculture provides a good model for the investigation of microvascular responses in the developing brain.

Animals↗
PubMed1996

Intraventricular hemorrhage in the preterm infant.

Intraventricular hemorrhage (IVH) is a common neonatal morbidity among premature infants which is diagnosed by cranial ultrasound in the newborn special care unit. Although very premature infants are more likely to experience the highest grades of hemorrhage, a number of perinatal and postnatal events have been shown to be associated with its occurrence. Factors such as vaginal delivery, labor, and intrapartum asphyxia have been associated with early onset of hemorrhage, whereas antenatal exposure to steroids may be protective. Respiratory Distress Syndrome has also been associated with hemorrhage. Since infants with a history of IVH have increased mortality rates and are at increased risk of seizures, periventricular leukomalacia, hydrocephalus, and neurodevelopmental handicap, many investigators have studied management techniques and pharmacologic interventions to decrease the incidence of IVH, including muscle paralysis, phenobarbital, Vitamin E, indomethacin, ethamsylate and surfactant. Our investigations have shown that low dose indomethacin (0.1 mg/kg i.v.) at 6-12 postnatal hours and every 24 h for two more doses decreases the incidence of all grades of IVH within the first 5 days of life. Although tremendous progress has been made in the understanding of the pathogenesis and prevention of IVH, innovative animal and human studies are needed to further reduce the incidence of this important neonatal morbidity.

Animals↗
PubMed1996

Neurodevelopmental outcome at 36 months' corrected age of preterm infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial.

OBJECTIVES: Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelopmental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA). METHODS: We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA. RESULTS: Three hundred eighty-four of the 431 infants survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean +/- SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 +/- 18.92, compared with 85.0 +/- 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo. CONCLUSIONS: Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.

Cerebral Hemorrhage↗
PubMed1995

Prevention of intraventricular hemorrhage in preterm infants.

Prematurely born infants with intraventricular hemorrhage (IVH) suffer significant morbidity and mortality, particularly those infants with high grade hemorrhage. The more premature infants have a higher incidence, experiencing more severe IVH. Early onset IVH is also likely to be severe and to progress to a higher grade. The etiology of intraventricular hemorrhages is clearly multifactorial, with differing sets of risk factors for early onset and later occurring hemorrhage. Prevention requires multilayered strategies, both prenatal and postnatal. These strategies are discussed in detail, highlighting unresolved controversies. Certain recommendations for prevention can be made. These include efforts to prevent preterm delivery, transfer of high risk mothers to tertiary care centers and antenatal maternal steroid use. Postnatally, the importance of optimal resuscitation and neonatal care practices is stressed, particularly those which minimize cerebral blood flow fluctuation. Postnatal indomethacin use should be considered in most infants. Further investigation of other strategies is necessary, including multicenter randomized trials to further evaluate antenatal pharmacologic agents, as well as the relative efficacy of different modes of delivery. The different risk factors for early onset versus later onset IVH must be more clearly delineated. Most importantly, any strategy must include sustained neurodevelopmental followup.

Adrenal Cortex Hormones↗
PubMed1995

Germinal matrix microvascular maturation correlates inversely with the risk period for neonatal intraventricular hemorrhage.

The risk period for intraventricular hemorrhage (IVH) of the preterm neonate is the first 3-4 postnatal days. For infants of < 34 weeks' gestation, this risk period is independent of gestational age. We hypothesized that this risk period is attributable to the perinatal induction of maturation of the germinal matrix microvasculature and tested this hypothesis by examining changes in the classical ultrastructural features of the blood-brain barrier over the first ten postnatal days in the newborn beagle model for neonatal IVH. Newborn beagle pups (n = 6) were anesthetized and systemically perfused and the brains were removed and prepared for electron microscopic examination. Examination of electron micrographs from the germinal matrix of animals on the first, fourth and tenth postnatal days demonstrated no difference in perimeter lengths and capillary and endothelial cell areas; in contrast, luminal areas significantly decreased across postnatal age (P = 0.04). Significant increases were found in basement membrane area between days 1 and 4 (P = 0.01) and tight junction length (day 1 vs. day 10, P = 0.02). In addition, on day 1, 19% of germinal matrix capillary perimeter was determined not to be covered by supporting cell processes, while by day 10, only 5% was bare. In contrast, the microvessels of the white matter exhibited no changes in these parameters during these three time points. These studies are consistent with the concept that basal lamina deposition and organization precede increases in endothelial cell tight junction formation and coverage by supporting cells.

Animals↗
PubMed1995

Antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants.

OBJECTIVE: The relationship between antenatal steroids, delivery mode, and early-onset intraventricular hemorrhage was examined in very-low-birth-weight infants. STUDY DESIGN: A total of 505 preterm infants (birth weight 600 to 1250 gm) were enrolled in a multicenter, prospectively randomized, controlled trial evaluating the efficacy of postnatal indomethacin to prevent intraventricular hemorrhage. All infants had echoencephalography between 5 and 11 hours of life. RESULTS: Seventy-three infants had intraventricular hemorrhage within the first 5 to 11 hours (mean age at echoencephalography 7.5 hours). Four hundred thirty-two infants did not have early intraventricular hemorrhage. There was less antenatal steroid treatment (19% vs 32%, p = 0.03) and more vaginal deliveries (71% vs 45%, p < 0.0001) in the group with early intraventricular hemorrhage. Of 152 infants who received antenatal steroids, those delivered by cesarean section had significantly less early-onset intraventricular hemorrhage than did those delivered vaginally (4% vs 17%, p = 0.02). Of the 353 not exposed to antenatal steroids, 10% of infants delivered by cesarean section and 22% delivered vaginally had early intraventricular hemorrhage (p = 0.003). CONCLUSION: These data are the first to suggest that both antenatal steroids and cesarean section delivery have an important and independent role in lowering the risk of early-onset intraventricular hemorrhage.

Cerebral Hemorrhage↗
PubMed1994

Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial.

We enrolled 61 neonates of 600 to 1250 gm birth weight with evidence of low-grade intraventricular hemorrhage at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that indomethacin (0.1 mg/kg given intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would prevent extension of intraventricular hemorrhage. Twenty-seven infants were assigned to receive indomethacin; 34 infants received saline placebo. There were no significant differences between the two groups in birth weight, gestational age, sex, Apgar scores, percentage of infants treated with surfactant, or distribution of hemorrhages at the time of the first cranial sonogram (echo-encephalogram). Within the first 5 days, 9 of 27 indomethacin-treated and 12 of 34 saline solution-treated infants had extension of their initial intraventricular hemorrhage (p = 1.00). Four indomethacin-treated and three saline solution-treated infants had parenchymal extension of the hemorrhage. Indomethacin was associated with closure of a patent ductus arteriosus by the fifth day of life (p = 0.003). There were no differences in adverse events attributed to indomethacin. We conclude that in very low birth weight infants with low grade intraventricular hemorrhage within the first 6 postnatal hours, prophylactic indomethacin therapy promotes closure of the patent ductus arteriosus and is not associated with adverse events, but does not affect the cascade of events leading to parenchymal involvement of intracranial hemorrhage.

Cerebral Hemorrhage↗
PubMed1994

Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial.

OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates. METHODS: We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed. RESULTS: There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.

Cerebral Hemorrhage↗
PubMed1993

Short-term response to dietary therapy in molybdenum cofactor deficiency.

Molybdenum cofactor deficiency was diagnosed in a 3-month-old girl who presented with microcephaly, developmental delay, severe irritability, and lactic acidosis. Dietary methionine restriction, with cysteine supplementation, was associated with moderate short-term clinical improvement, including a resumption in predicted head growth, modest developmental progress, and a reduction in irritability. Clinical relapse was associated with noncompliance of dietary therapy 2 months later. Urinary sulfite levels measured by commercial dipsticks were useful in following therapy. Molybdenum cofactor deficiency is probably frequently underdiagnosed due to the lack of specific clinical or laboratory features. Screening of infants at risk for the presence of urinary sulfites or serum hypouricemia, or both, is both rapid and inexpensive.

Acidosis, Lactic↗
PubMed1993

Infantile chorea following abrupt withdrawal of diazepam and pentobarbital therapy.

The acute onset of chorea was seen in a ten week-old male following abrupt cessation of a seven-day course of sedation with diazepam and pentobarbital. These movements slowly resolved over a six-day period and the infant was without neurologic sequelae one week after his chorea resolved. A cerebral MRI was normal. We speculate that the mechanism by which chorea may occur as a withdrawal phenomenon to benzodiazepine/barbiturate treatment is by a functional overactivity of the dopaminergic system in the basal ganglia.

Cardiac Catheterization↗
PubMed1993

Intraventricular hemorrhage and prematurity.

Intraventricular hemorrhage or hemorrhage into the germinal matrix tissues of the developing brain with possible rupture into the ventricular system and parenchyma remains a major problem of preterm neonates and is believed to be attributed to alterations in cerebral blood flow to a damaged germinal matrix capillary bed. Topics discussed in this article include germinal matrix anatomy and physiology, neuropathology, risk of hemorrhage, diagnostic imaging techniques, clinical manifestations, posthemorrhagic hydrocephalus, treatment, and outcomes.

Cerebral Hemorrhage↗
PubMed1992

Risk factors for early intraventricular hemorrhage in low birth weight infants.

Because earlier studies suggested that preterm infants with germinal matrix hemorrhage or intraventricular hemorrhage or both (GMH/IVH) present within the first 12 postnatal hours are at greatest risk for the development of high-grade hemorrhage and neurodevelopmental disability, we examined the risk factors for this insult among 229 neonates of 600 to 1250 gm birth weight in a multicenter study. All had echoencephalography (ECHO) within the first 11 hours and serially for the next 20 days; risk factor data were collected prospectively. Forty-three infants had GMH/IVH within the first 5 to 11 hours (mean age at ECHO 7.7 hours): 18 GMH and 21 grade II, 1 grade III, and 3 grade IV IVH. One hundred eighty-six infants did not have GMH/IVH at a mean age of 7.9 hours. Both groups of infants were similar in birth weight, gestational age, maternal risk factors, cord pH values, and surfactant therapy before ECHO. The group with early IVH had more vertex presentations than the group without early IVH (79% vs 55%, p = 0.043), less maternal tocolytic use (42% vs 60%, p = 0.029), and more vaginal deliveries (67% vs 44%, p = 0.005). In the first 21 days, severe IVH developed in 12 infants with early IVH and in 6 infants without early IVH (p < 0.001). There were more neonatal deaths (16% vs 6%, p = 0.035) and more deaths at any time during the primary hospitalization (23% vs 9%, p = 0.010) among the early IVH group than among the group without early IVH. Multivariate analysis indicated that the mode of delivery, fetal presentation, and birth weight were important and independent prognostic indicators of IVH.

Birth Weight↗
PubMed1992

Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.

BACKGROUND AND PURPOSE: Although indomethacin has been demonstrated to prevent germinal matrix and intraventricular hemorrhage in clinical and animal studies, the mechanism of action of this agent to prevent hemorrhage remains unclear. Previous studies have demonstrated both that the microvessels in the germinal matrix of newborn beagle pups undergo basement membrane maturation during the first 4 postnatal days and that indomethacin may promote laminin deposition in tumor cell culture systems. METHODS: We employed the newborn beagle pup model to test the hypothesis that indomethacin may stimulate laminin deposition in germinal matrix microvessels. Newborn pups were randomized to receive either 0.1 mg/kg/dose i.p. indomethacin or an equal volume of saline diluent. Pups received doses of study medication once a day for 1, 2, or 3 days and were studied on postnatal days 1, 2, 3, or 4. Pups were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. RESULTS: Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density among the postnatal ages studied; similarly, there were no differences in vessel density between saline- and indomethacin-treated animals at any postnatal age. Quantification of germinal matrix stained intensity by confocal microscopy demonstrated significant increases in indomethacin-treated pups for both laminin staining at postnatal days 2 (p = 0.05) and 3 (p = 0.0009) and type V collagen staining at postnatal day 2 (p = 0.011). Although staining for beta 1 integrins increased across postnatal ages, there were no differences between saline- and indomethacin-treated animals. CONCLUSIONS: These data suggest that indomethacin may stimulate basement membrane deposition in the germinal matrix microvessels of newborn beagle pups to prevent germinal matrix and/or intraventricular hemorrhage.

Animals↗
PubMed1991

Beagle pup germinal matrix maturation studies.

Intraventricular hemorrhage, or hemorrhage into the germinal matrix tissues of the developing brain, remains a common problem of preterm infants. The "risk period" for this insult is the first 3-4 postnatal days. We hypothesized that this risk period for hemorrhage is related to rapid perinatal maturation of the germinal matrix vasculature and employed the newborn beagle pup model for the study of this maturation. Newborn beagle pups (n = 30) were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density between postnatal days 1 and 4. Germinal matrix sections were also stained for antibodies to alpha-smooth muscle actin, collagen IV, collagen V, desmin, factor VIII-related antigen, fibronectin, glial fibrillary acidic protein, laminin, transferrin, and vimentin. Vasculature staining by alpha-smooth muscle actin was not noted until postnatal day 10, and differential staining was detected for antibodies to laminin and collagen V. Quantification of staining intensity by confocal microscopy demonstrated a significant increase in both extracellular matrix components at postnatal day 4 compared with day 1 (p less than 0.05 for both). These basement membrane proteins may add sufficient structural integrity to germinal matrix vessels to prevent capillary rupture and thus intraventricular hemorrhage.

Aging↗