ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Children born preterm and of very low birth weight have an increased incidence of learning difficulties, but little is known about the specific nature of their cognitive deficits and the underlying neuropathology. We hypothesized that their vulnerability to hypoxic, metabolic, and nutritional insults would lead to reduced hippocampal volumes and to deficits in memory because of the role of the hippocampus in this domain of cognition. Neuropsychological and magnetic resonance imaging methods were used to investigate this hypothesis in adolescents born preterm (≤30 wk gestation,n= 11) or full-term (n= 8). The preterm group had significantly smaller hippocampal volumes bilaterally, despite equivalent head size, and showed specific deficits in certain aspects of everyday memory, both on objective testing and as indicated by parental questionnaires. The preterm group also had a specific deficit in numeracy. The reduced hippocampal volumes and deficits in everyday memory have previously been unrecognized, but their prevalence in a group of neurologically normal children is striking.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Placental abnormalities reflect antenatal disease processes that may interact with other perinatal risk factors to affect long-term outcome. We performed a nested case control analysis of placental and clinical risk factors associated with neurologic impairment (NI) at 20-mo corrected age (60 cases and 59 controls) using data collected in a prospective study of very low birth weight (less than 1500 g) infants born between 1983 and 1991. In a preliminary analysis we explored the relationship between clinical infection and histologic chorioamnionitis (CA). Only histologic CA with a fetal vascular response correlated with either clinical CA or early onset neonatal sepsis. We then assessed the relative contribution of the nine risk factors (four placental and five clinical) associated with NI at the univariate level by multiple logistic regression. Three risk factors were independent predictors of NI: severe cranial ultrasound abnormalities (odds ratio 13.6, 95% confidence intervals 4.5–66.7), multiple placental lesions (odds ratio 13.2, 95% confidence intervals 1.3–137.0), and oxygen dependence at 36 wk (odds ratio 4.2, 95% confidence intervals 1.2–14.6). Finally, a series of logistic regressions was conducted with the dependent variable changing as we-moved back along the causal chain to explore the relationships between risk factors operating at different stages. This analysis suggested that antenatal variables that were not independent predictors of NI by multiple logistic regression exerted their effects through the following intermediate pathways: fetal grade 3 histologic CA via chorionic vessel thrombi, clinical CA via grade 3 villous edema, and grade 3 villous edema via severe cranial ultrasound abnormalities.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Iatrogenic tolerance and physical dependence have been documented in human neonates and infants infused with fentanyl or morphine i.v. to maintain continuous analgesia and sedation during extracorporeal membrane oxygenation (ECMO) and mechanical ventilation for the treatment of life-threatening pulmonary diseases. Using postnatal d 17 infant rats, the hypothesis was tested that sedative tolerance accompanies tolerance to fentanyl analgesia in the tail-flick test. Postnatal d 14 infant rats remained naive or received osmotic minipumps infusing saline (1 &mgr;L/h) or fentanyl citrate (60 &mgr;g·kg–1h–1). Seventy-two hours later, fentanyl’s antinociceptive potency was reduced 3.1-fold in fentanyl-infused rats. Conscious sedation and deep sedation were examined with the cliff-avoidance and the righting-reflex procedures, respectively. Fentanyl-infused infants were tolerant to both the conscious and deep sedative effects of fentanyl. Another hypothesis tested was that very high receptor intrinsic activity opioids are less likely to produce tolerance, or to be cross-tolerant to other opioids. Dihydroetorphine is 5 000 to 10 000 times more potent than morphine. However, fentanyl-infused infant rats were cross-tolerant to the analgesic and sedative effects of dihydroetorphine. Interestingly, dihydroetorphine’s analgesic efficacy was significantly reduced to a maximum analgesic efficacy (Emax) value of 40% maximum possible effect (MPE). Another concern was whether fentanyl tolerance would generalize to another class of sedatives, the benzodiazepines. This was especially relevant considering the widespread use of benzodiazepines like midazolam in ECMO and mechanical ventilation. Midazolam elicited no analgesia in the tail-flick test. Furthermore, fentanyl-tolerant rats were not cross-tolerant to the conscious or deep sedative effects of midazolam.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

An association between chorioamnionitis and periventricular leukomalacia has been reported in human preterm infants. However, whether this link is causal has not been convincingly established, and the underlying molecular mechanisms remain unclear. The objective of this study was to establish a reproducible model of cerebral white matter disease in preterm rabbits after intrauterine infection.Escherichia coliwas inoculated into both uterine horns of laparotomized pregnant rabbits when gestation was 80% complete. The fetuses were delivered by cesarean section and killed 12, 24, or 48 h after the inoculation. Programmed cell death in the white matter was evaluated by hematoxylin-eosin-saffron staining andin situfragmented DNA labeling (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). In a first group of 14 pregnant rabbits not treated with antibiotics, all fetuses delivered 48 h after inoculation were stillborn, whereas fetuses extracted 12 or 24 h after inoculation were alive. No significant cell death was detected in the live fetuses compared with the control noninfected rabbits. In a second group of five pregnant rabbits treated with ceftriaxone initiated 24 h after the inoculation and continued until cesarean section was performed 48 h after inoculation, 13 fetuses were alive, but all showed evidence of extensive programmed cell death in the white matter by hematoxylin-eosin-saffron staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. White matter damage became histologically detectable only 48 h after inoculation. Three of the 13 brains displayed periventricular white matter cysts mimicking human cystic periventricular leukomalacia. The high reproducibility of white matter damage in our model should permit further studies aimed at unraveling the molecular mechanisms of periventricular leukomalacia.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Enzyme replacement therapy (ERT) in the MPS VI cat is effective at reducing or eliminating pathology in most connective tissues. One exception is that cartilage and chondrocytes remained distended with extensive lysosomal vacuolation after long-term, high-dose ERT. In this study, we demonstrate that recombinant human N-acetylgalactosamine-4-sulphatase (4S) is taken up by chondrocytes via a mannose-6-phosphate-dependent mechanism and is effective at removing MPS storage.In vitro,the penetration of 4S into articular cartilage is low (partitioning coefficient = 0.06) and i.v. administered enzyme does not distribute significantly into articular cartilagein vivo. To alter the tissue distribution of 4S, the enzyme was coupled to ethylene diamine or poly-L-lysine, increasing its overall charge and diffusion into cartilage, and the dosing frequency of unmodified 4S was increased. Modification resulted in active 4S that maintained its ability to correct MPS storage and increased the partitioning coefficient of 4S into cartilage by 77% and 50% for ethylene diamine and poly-L-lysine, respectively. However,in vivoERT studies demonstrated that response to therapy was not significantly improved by either the enzyme modifications or change to the dosing regimen, when compared with ERT with unmodified enzyme. Distribution experiments indicated the majority of enzyme is taken up by the liver irrespective of modification. To optimize therapy and improve the amount of enzyme reaching cartilage and other tissues demonstrating poor uptake, it may be necessary to bypass the liver or prolong plasma half-life so that proportionately more enzyme is delivered to other tissues.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID