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Biomedical subjects

L R Ment

Publications and source records attributed to L R Ment.

99 records · Page 6Linked to original sources

Predictors of success for drug discontinuation following neonatal seizures.

Guidelines for the discontinuation of antiepileptic drugs in neonatal seizures are not well defined. Some studies suggested possible criteria for antiepileptic drug discontinuation but no precise criteria have emerged. We performed a retrospective analysis of 58 infants with neonatal seizures during a 3 year period. Antiepileptic drugs were discontinued when patients were seizure-free for 3 months, had normal electroencephalography initially or at subsequent examination, and had a nonfocal examination. Normal initial electroencephalography was demonstrated to be a reliable predictor for discontinuing antiepileptic drugs successfully in 18 of 22 term infants; normal subsequent electroencephalography was a reliable predictor of successful discontinuation of antiepileptic drugs in 9 of 10 premature infants.

Anticonvulsants↗

Beagle puppy model of perinatal asphyxia: alterations in cerebral blood flow and metabolism.

Perinatal asphyxia remains a major cause of neurodevelopmental handicap. The neuropathologic and clinical sequelae of perinatal asphyxia are likely attributable to alterations in cerebral blood flow (CBF) to the developing brain with uncoupling of CBF and metabolism. The newborn beagle puppy model was used to study the control of CBF in physiologic and pathologic conditions in the developing brain. Pups, 2-10 days of age, were randomized to asphyxial insult (i.e., ventilator lines clamped for 5 min) or no insult. In the first series, pups underwent radioactive microsphere determinations of CBF immediately prior to insult (t = 0), at the end of insult (t = 5), and after 60 min of observation (t = 65). In the second series, utilizing a 2.0 tesla superconducting magnet, pups underwent continuous serial in vivo 31P nuclear magnetic resonance spectral analysis of cerebral hemispheric metabolic state. Animals exposed to insult had significant alterations in PO2, PCO2, pH, and mean arterial pressure at the end of insult compared to control pups (all pups: p less than 0.001). Serial CBF data demonstrated decreases in flow in cortical gray and white matter regions during insult and return to baseline 1 hour later; brainstem structures were hyperemic during insult. Analysis of phosphorylated metabolites inorganic phosphorus (Pi), phosphocreatine (PCr), and ATP demonstrated that during insult both the PCr/Pi and ATP/Pi ratios were depressed but by 20-30 min following insult, these ratios of cerebral phosphorylated metabolites had almost returned to baseline values. These data demonstrate that even after a severe asphyxial episode which results in electrocerebral silence, CBF and metabolism may return to normal.

Acid-Base Equilibrium↗

Beagle puppy model of perinatal asphyxia: blockade of excitatory neurotransmitters.

The N-methyl-D-aspartate receptor antagonist MK801 has been reported to prevent neuronal change in models of ischemia in adult animal systems. We studied the hypothesis that blockade of the N-methyl-D-aspartate receptor would prevent the depression of cerebral high-energy phosphates found in perinatal asphyxia without producing alterations in cerebral blood flow, and thus prevent neuropathologic damage. Newborn beagle puppies were anesthetized, tracheotomized, ventilated, and randomized to asphyxial insult (I = discontinuation of ventilatory support for 5 min) or no insult (NI) and drug treatment with MK801 (10 mg/kg intravenously) or an equal volume of saline (S). Puppies received MK801 or saline 15 min prior to I/NI. In S/I pups during insult, blood flow increased to brainstem structures but decreased elsewhere. MK801 had no effect on cerebral blood flow in either control or insulted puppies. 1H NMR studies demonstrated no effect of the MK801 on NI brains. Phosphocreatine levels were 1.7 +/- 0.1, 0.6 +/- 0.1, and 0.9 +/- 0.1 mmole/kg (mean: +/- S.D.) for the S/NI, S/I, and MK801/I pups, respectively. Cerebral lactate was 1.3 +/- 0.2, 3.0 +/- 0.7, and 2.0 +/- 0.4, respectively. The pH fell 0.8 units in the S/I puppies, compared to 0.4 units in the MK801/I puppies. We conclude that pretreatment with the N-methyl-D-aspartate receptor antagonist MK801 in part protects the developing brain against severe metabolic insult.

Animals↗

Cassette electroencephalographic recording of neonates with apneic episodes.

To evaluate the practical importance of seizures as a cause of neonatal apnea, we obtained extended cassette electroencephalographic recording for periods as long as 24 hours from 50 neonates experiencing apneic episodes unassociated with clinical seizure activity. Electroencephalographic recording through definite apneic episodes was obtained in 37 neonates; a total of 153 episodes were detected. None was associated with electroencephalographic seizure activity, although one term neonate without documented apneic episodes had seizure activity detected by cassette electroencephalography and may have had apneic seizures. The episodic apnea and bradycardia commonly encountered in preterm neonates is unlikely to be a manifestation of seizure activity, and extended electroencephlographic monitoring of such patients is of low yield.

Cerebral Cortex↗

Perinatal cerebral insults: hemorrhage and ischemia.

The incidence of major neurodevelopmental handicaps in the survivors of newborn special care has remained essentially unchanged over the past decade despite the development of sophisticated perinatal care. Preterm infants with parenchymal involvement of intraventricular hemorrhage and neonates of all gestational ages with cerebral infarction are believed to be at higher risk for both neurologic and developmental abnormalities than infants without these problems. Both lesions are thought secondary to alterations in cerebral blood flow to the developing brain, and many infants demonstrate evidence for both hemorrhage and ischemic insult.

Brain Ischemia↗

Observations of the dynamics of ionic potassium-38 in brain.

Short time course potassium dynamics in brain were investigated in the cat. 38K (T1/2 = 7.6m) was prepared on the BNL 60" cyclotron by the 40Ar(p, 3n)38K reaction. Positron decay in brain was measured by the limited angle of view positron camera (LAPC). Radioactivity corrected for physical decay following intravenous bolus injection of 38K showed an initial peak followed by a washout phase with a subsequent monotonic increase. The slope of the washout phase was linearly related to PaCO2 and the subsequent monotonic increase paralleled the arterial concentration of the tracer. No significant changes in 38K radioactivity were determined following coma producing levels of phenobarbital or seizure producing doses of potassium penicillin as compared to control.

Animals↗

Beagle pup model of perinatal asphyxia: nimodipine studies.

Calcium antagonists may be of significant benefit in the pharmacotherapy of cerebral ischemia, possibly by improving postischemic cerebral blood flow (CBF). This study evaluated the effects of the calcium antagonist nimodipine on CBF in a newborn beagle pup model of perinatal asphyxia lasting 5 minutes. Immediately after the asphyxial episode, nimodipine (2 micrograms/kg/min) or saline was infused for 10 minutes, following which [14C]iodoantipyrine determinations of CBF were performed. In noninsulted pups, nimodipine caused both significant decreases in CBF to cortical and deep gray structures as well as a decrease in mean arterial blood pressure (MABP) (p less than 0.05). In insulted pups, nimodipine similarly decreased MABP (p less than 0.001) and CBF to cortical and deep gray matter regions. Nimodipine appeared to have no effect on arterial blood gases and EEG tracings in either insulted or noninsulted pups. Although nimodipine may be shown to improve neurologic outcome in asphyxiated newborn infants, the limits of this study do not show the mechanism to be that of improving CBF.

Animals↗

The relation of proton activation of brain to cerebral blood flow.

The interaction of brain with high energy protons produces positron emitting nuclides. The present study examines the response of the decay events to oxygen-15 induced by such activation in brain to alterations of cerebral blood flow as measured by a limited angle planar positron camera. Decay events correlate directly to the cerebral blood flow. The interaction of brain with high energy protons appears to offer an alternative means for the delivery of a freely diffusible tracer into brain.

Animals↗

Cerebral blood flow determinations by positron emission tomography.

Multiple approaches are available to measure global and regional cerebral blood flow. The inert gas method of Kety-Schmidt provides the mathematical basis for essentially all of these methods with the exception of microspheres. The preferred method depends largely upon the type of information to be obtained. The preferred method depends largely upon the type of information to be obtained. The three essential problems in cerebral blood flow measurement are establishing reliable cerebral blood flow measurements in pathological processes, the relation of this flow to metabolism, and the clinical application of cerebral blood flow measurements in man for the investigation of a wide variety of significant disease processes including ischemia and intracranial hypertension.

Autoradiography↗