Biomedical subjects

J Y Yager

Publications and source records attributed to J Y Yager.

32 records · Page 2Linked to original sources

PubMed1993

Neuropathologic aspects of hypothermic circulatory arrest in newborn dogs.

A model of hypothermic circulatory arrest with recovery has been developed in the newborn dog. Eleven puppies were anesthetized with halothane, paralyzed and artificially ventilated with 70% nitrous oxide -30% oxygen to paO2 > 60 mm Hg, paCO2 = 33-42 mm Hg and pHa = 7.35-7.42. Animals were surface cooled to 20 degrees C, following which cardiac arrest was effected with i.v. KCl. Dogs remained asystolic without ventilation for 1.0, 1.5 or 1.75. Resuscitation was accomplished with closed-chest compression, mechanical ventilation, i.v. epinephrine and NaHCO3, and rewarming to 37 degrees C. Thereafter, the puppies were allowed to recover from anesthesia and maintained for either 18-22 h (n = 9) or 72 h (n = 2), at which time they underwent perfusion-fixation of their brains for pathologic analysis. Of the total, four out of four puppies arrested for 1.0 h exhibited no brain damage, including one recovered for 72 h; whereas one out of three and four out of four puppies arrested for 1.5 and 1.75 h, respectively, showed brain damage predominantly of the cerebral cortex but also of the basal ganglia and amygdaloid nucleus. The hippocampus was spared, even in a 1.75-h-arrested animal which was maintained for 72 h. No differences in pre- or post-arrest systemic blood pressure, heart rate, or acid-base balance were observed between the brain damaged and undamaged animals except for the single damaged animal arrested for 1.5 h, for which the blood pressure prior to cardiac arrest and during recovery was the lowest of all survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Astrocyte maturation and susceptibility to ischaemia or substrate deprivation.

We demonstrate that immature astrocytes die much earlier than mature astrocytes when substrate is deprived in the presence of oxygen. In contrast, mature astrocytes die much earlier than immature astrocytes when substrate is deprived in the absence of oxygen. These observations correlate well with the recent findings that the newborn rodent brain is more susceptible to damage from lack of substrate than from lack of oxygen. The basis for this susceptibility of immature astrocytes to substrate deprivation in the presence of oxygen is not clear, but perhaps is related to the ability of the cell to scavenge free radicals.

Animals↗

PubMed1992

Cerebral energy metabolism during hypoxia-ischemia and early recovery in immature rats.

Persistent alterations in cellular energy homeostasis may contribute to the brain damage that evolves from perinatal cerebral hypoxia-ischemia. Accordingly, the presence and extent of perturbations in high-energy phosphate reserves were analyzed during hypoxia-ischemia and the early recovery period in the immature rat. Seven-day postnatal rats were subjected to unilateral common carotid artery ligation and hypoxia with 8% oxygen at 37 degrees C for 3 h, an insult that produces damage (selective neuronal necrosis or infarction) of the cerebral hemisphere ipsilateral to the common carotid artery ligation in 92% of animals. Rat pups were quick frozen in liquid nitrogen during hypoxia-ischemia and at 10, 30, and 60 min and 4 and 24 h of recovery for enzymatic, fluorometric analysis of phosphocreatine (PCr), creatine, ATP, ADP, and AMP. During hypoxia-ischemia, PCr, ATP, and total adenine nucleotides were decreased by 87, 72, and 50% of control, respectively. During recovery, PCr, ATP, and total adenine nucleotides exhibited a rapid (within 10 min) although incomplete and heterogeneous recovery that persisted for at least 24 h. Mean values for PCr remained between 55 and 85% of control, whereas ATP values remained between 57 and 67% of control. Individual ATP values were inversely related to tissue water content at 10 min of recovery, indicating a close correlation between failure of energy restoration and the extent of cerebral edema as a reflection of brain damage. Thus high-energy phosphate reserves display lingering alterations during recovery from hypoxia-ischemia. The interanimal variability in energy restoration presumably reflects the spectrum of brain damage seen in this model of perinatal cerebral hypoxia-ischemia.

Adenine Nucleotides↗

PubMed1992

Effect of insulin-induced and fasting hypoglycemia on perinatal hypoxic-ischemic brain damage.

Experiments in adult animals have indicated that hyperglycemia accentuates whereas hypoglycemia ameliorates hypoxic-ischemic brain damage. To determine whether hypoglycemia is protective or deleterious to the perinatal brain subjected to hypoxia-ischemia, 7-d postnatal rats were rendered hypoglycemic either by receiving an s.c. injection of insulin or fasting for 12 h. All rat pups underwent unilateral common carotid artery ligation followed by exposure to 8% oxygen-balance nitrogen at 37 degrees C for 2 h. Control animals (no insulin or fasting) received s.c. injections of normal saline. Mean blood glucose concentrations were 5.4 +/- 0.1, 4.3 +/- 0.2, and 3.4 +/- 0.1 mmol/L for control, insulin, and fasted animals, respectively. Blood beta-hydroxybutyrate concentrations were identical (0.5 +/- 0.1 mmol/L) for control and insulin-treated animals, but more than doubled in concentration in the fasted animals (p less than 0.001). Mortality rates during hypoxia-ischemia were higher in the insulin-treated animals (30%) than in either the fasted (4%) or control (0%) animals (p less than 0.05). Fasted animals showed a significant reduction in hypoxic-ischemic brain damage as compared with either the insulin-treated or control animals. Insulin-treated animals were not significantly different from controls. The findings indicate that 1) insulin induced hypoglycemia does not provide a protective effect on perinatal hypoxic-ischemic brain damage, as in adults; and 2) fasting adequate to produce hypoglycemia and ketonemia improved neuropathologic outcome.

Animals↗

PubMed1992

Cerebral oxidative metabolism during hypothermia and circulatory arrest in newborn dogs.

To ascertain the alterations in cerebral oxidative and energy metabolism that occur during hypothermic circulatory arrest, nitrous oxide-anesthetized, paralyzed, and artificially ventilated newborn dogs were surface cooled to 18-20 degrees C, after which their hearts were arrested with KCl. At 10, 30, 60, and 105 min of circulatory arrest, their brains were prepared by in situ freezing for the regional analysis of glycolytic intermediates and high-energy phosphate reserves. Hypothermia alone was associated with optimal preservation of labile metabolites in brain, even in caudal brainstem and cerebellum, compared with barbiturate-anesthetized littermates. After onset of hypothermic circulatory arrest, glucose decreased progressively in cerebral cortex, caudate nucleus, hippocampus, and subcortical white matter to negligible levels by 30 min. Pyruvate increased transiently (+50%) at 10 min, whereas lactate increased and plateaued (10-11 mmol/kg) at 30 min. The disproportionate increases in pyruvate and lactate resulted in a progressive rise in the lactate/pyruvate ratio. Phosphocreatine fell precipitously to < 0.5 mmol/kg in all structures, with a preservation of ATP for the first 10 min of cerebral ischemia. Thereafter, ATP decreased to < 0.1 mmol/kg in cerebral cortex and between 0.1 and 0.2 mmol/kg in caudate nucleus, hippocampus, and white matter. Total adenine nucleotides (ATP+ADP+AMP) were partially depleted by 30 min in the gray matter structures but were unchanged from control for 60 min in white matter. The findings showed a direct correlation between preservation of cerebral energy stores during hypothermic circulatory arrest and the selective resistance of subcortical white matter to ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Neuropathology of remote hypoxic-ischemic damage in the immature rat.

This study was undertaken to determine: (a) the duration of hypoxia required to produce brain damage in immature rats with unilateral carotid artery ligation (Levine technique); (b) the regions of immature brain most vulnerable to hypoxia-ischemia (HI); and (c) the neuropathology of the remote HI insult. To this end, 7-day postnatal rats, subjected to unilateral carotid artery ligation combined with hypoxia of varying durations (45, 60, 75 or 90 min), were killed at 30 days of postnatal age and their brains examined by light microscopy. The results indicated that a longer duration of HI was more likely to produce brain lesions and that the extent and severity of the lesions closely correlated with the length of HI. Shorter intervals of HI primarily damaged the cerebral cortex and hippocampus, while longer periods resulted in more extensive damage and were often associated with cavitary lesions of the cerebral hemisphere. Comparison of HI brain damage produced by the Levine technique in immature and adult rats suggested that in immature rats: (a) the cavitary lesions were common; (b) the non-cavitary cortical lesions had a tendency to show a vertical band-like distribution - a pattern never seen in adults; and (c) the lesions often showed mineralization. The similarities between these experimentally produced HI cerebral lesions and those observed in the developing human brain, such as ulegyria and porencephaly, are discussed.

Amygdala↗

PubMed1991

Inter-observer agreement in assessing comatose children.

Inter-observer agreement was evaluated for twelve items used in the neurological assessment of comatose children. Data were obtained prospectively on fifteen patients examined independently by two observers in a double-blind fashion. Observer variability was measured by using the Disagreement Rate and Kappa statistic. The Disagreement Rate ranged from 0.01 to 0.12 for all items. Values for Kappa statistic were generally in accordance with those for Disagreement Rate. The data suggest fair to almost perfect inter-observer agreement for the items used to assess comatose children in this study.

Adolescent↗

PubMed1991

Cerebral oxidative metabolism and redox state during hypoxia-ischemia and early recovery in immature rats.

Intracellular pH (pHi) and cytoplasmic and mitochondrial oxidation-reduction (redox) states of cerebral tissue were examined in relation to perturbations of glycolytic and tricarboxylic acid cycle intermediates and of high-energy phosphate reserves during hypoxia-ischemia and the early recovery period in the immature rat. Seven-day postnatal rats underwent unilateral common carotid artery ligation and exposure to 8% O2 for 3 h, after which they were quick frozen in liquid N2 at the terminus of hypoxia-ischemia and at 10, 30, 60, and 240 min of recovery for enzymatic fluorometric analysis of cerebral metabolites. During hypoxia-ischemia, concentrations of glucose and alpha-ketoglutarate in the cerebral hemisphere ipsilateral to the carotid artery occlusion were depleted to 10 and 70% of control, respectively; pyruvate was unchanged. During recovery, glucose, pyruvate, and alpha-ketoglutarate increased above their respective control values. Calculated pHi decreased from 7.0 (control) to 6.6 during hypoxia-ischemia and normalized by 10 min of recovery. The cytoplasmic NAD+/NADH ratio decreased (increased reduction) to 50% of control during hypoxia-ischemia and remained in the reduced state throughout 4 h of recovery. Paradoxically, mitochondrial NAD+/NADH was oxidized at the terminus of hypoxia-ischemia. The mitochondrial oxidation which developed during hypoxia-ischemia presumably results from a limitation of cellular substrate (glucose) supply, which in turn leads to a depletion of high-energy phosphate reserves, culminating in brain damage.

Animals↗

PubMed1990

Coma scales in pediatric practice.

Interobserver variability for six coma scales was assessed prospectively on a sample of 15 comatose children, by two physicians, in a double-blind fashion. The six scales were the Glasgow Coma Scale, the Simpson and Reilly Scale, the Children's Coma Score, the Children's Orthopedic Hospital and Medical Center Scale, the Jacobi Scale, and the 0 to IV Scale. Interobserver variability was measured by using disagreement rate and the kappa statistic. The results from both methods were generally concordant. The disagreement rate for the various items in the different scales ranged from a high of 0.20 to a low of 0.03. The disagreement rate was greater than 0.10 for verbal responses in the Children's Coma Score and Glasgow Coma Scale and for both items in the Children's Orthopedic Hospital and Medical Center Scale. The disagreement rate was 0.10 or less for the 0 to IV Scale and for all items in the Simpson and Reilly and Jacobi scales. The relatively high interobserver agreement for these scales makes them more suitable for the pediatric setting than the other three scales, since good agreement is essential for interpreting data reliably, both in clinical practice and for research.

Adolescent↗

PubMed1988

Sublingual lorazepam in childhood serial seizures.

Sublingual lorazepam was successful in controlling serial seizures in ten children. There was both intrasubject and intersubject variability in the effective dose, which ranged from about 0.05 mg/kg to 0.15 mg/kg. Side effects were minimal and consisted of drowsiness, unsteadiness, nausea, and hyperactivity. Sublingual lorazepam is an easy and effective way to treat serial seizures at home.

Administration, Sublingual↗

PubMed1988

CT-scan findings in an infant with glutaric aciduria type I.

An infant presented at three weeks of age with a rapidly enlarging head and hypertonicity. The diagnosis of glutaric aciduria type I (GAI) was confirmed by the absence of the enzyme glutaryl-CoA dehydrogenase in fibroblast culture. A CT scan at that time showed diffuse attenuation of cerebral white-matter. Scans at five and 10 months of age showed loss of white-matter volume and diffuse cerebral atrophy, most prominent in the frontal and temporal regions. GAI should be considered in the differential diagnosis of infants and children with neurological dysfunction who have CT-scan findings of white-matter attenuation and/or cerebral atrophy, most prominent in the frontal and temporal regions, and/or changes in the basal ganglia or thalamus.

Amino Acid Metabolism, Inborn Errors↗

PubMed1988

Status epilepticus in children.

We have prospectively reviewed the data on 52 children who presented with status epilepticus. Thirty-four (65%) of the 52 had not had seizures before. Children who were previously abnormal were more likely to present with partial status epilepticus or to have seizures greater than 60 minutes than those who were previously normal. The median age (24 months) of those who presented with status epilepticus was the same as that of children with seizures of shorter duration. The causes were equally distributed among the idiopathic, acute encephalopathic and chronic encephalopathic groups. Three children died and 13 (28%) were left with neurological sequelae. The outcome was favorable for those in the idiopathic category.

Anticonvulsants↗

PubMedDate not supplied

Glucose, lactic acid, and perinatal hypoxic-ischemic brain damage.

Investigations suggest that hyperglycemia, superimposed on hypoxia-ischemia or cerebral ischemia, accentuates brain damage in adult experimental animals and humans, but not in immature animals. Fundamental differences in the immature and adult brain, which account for the age-specific paradox, are discussed. Based on currently available data, we recommend that glucose supplementation not be curtailed during labor and delivery of asphyxiated human infants; on the contrary, glucose therapy may substantially reduce hypoxic-ischemic brain damage.

Animals↗

PubMedDate not supplied

Nature, time-course, and extent of cerebral edema in perinatal hypoxic-ischemic brain damage.

To ascertain the nature, time-course, and extent of the cerebral edema that accompanies perinatal hypoxic-ischemic brain damage, 7-day postnatal rats were subjected to unilateral right common carotid artery ligation followed by exposure to hypoxia with 8% oxygen for up to 3 hours. Some rat pups were sacrificed during hypoxia-ischemia or recovery for determination of cerebral hemispheric water content and percentage of brain swelling. Other animals were sacrificed and their brains processed either for determination of cerebral cortical edema and infarct volume or for horseradish peroxidase staining. The results indicated that cerebral edema occurs even during the course of hypoxia-ischemia and that the extent and duration of edema formation during the recovery period is dependent upon the severity of tissue injury. The data also disclosed a direct, linear correlation between infarct volume and the extent of cerebral edema. Accordingly, the greater the severity of cerebral edema, the proportionately greater the extent of infarction. Horseradish peroxidase staining, a reflection of vasogenic edema, occurred in 17 of 19 brains in a distribution which corresponded closely to the distribution of neuropathologic alterations observed histologically. The findings indicate that cerebral edema can occur in the absence of consequent infarction and that when infarction does occur, the associated edema contributes little or nothing to the severity of the ultimate brain damage.

Analysis of Variance↗