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Biomedical subjects

S Ashwal

Publications and source records attributed to S Ashwal.

12 recordsLinked to original sources

The persistent vegetative state in children: report of the Child Neurology Society Ethics Committee.

Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% believed that this applied to infants younger than 2 months and 70% in the 2-month to 2-year group; (2) a period of 3 to 6 months was believed to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4.1; 2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% "never" withhold fluid and nutrition from infants and children in a PVS and 28% "always" give medication for pain and suffering.(ABSTRACT TRUNCATED AT 250 WORDS)

Advisory Committees

Hypoxia inhibits calcium influx in rabbit basilar and carotid arteries.

We examined the hypothesis that hypoxia inhibits Ca2+ influx in isolated rabbit common carotid, internal carotid, and basilar arteries. In arteries mounted for measurement of isometric tension and exposed to 122 mM K+ in Ca(2+)-free Krebs, cumulative addition of Ca2+ produced Ca(2+)-force relations that were right-shifted by hypoxia (PO2 approximately 15 Torr) with no decrease in maximum force attained. In arteries precontracted with 122 mM K+, exposure to hypoxia produced relaxations whose rates and magnitudes were enhanced by reductions in bath Ca2+ from 8.0 to 0.8 mM. Using an ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid method for 3-min 45Ca influx measurements, modified for use in rabbit basilar and carotid arteries, we found that resting levels of Ca2+ influx (mumol.min-1.kg dry wt-1) were significantly higher in basilar (67 +/- 1, n = 10) than in internal carotid (27 +/- 1, n = 12) or common carotid (33 +/- 1, n = 12) arteries. K+ stimulation increased Ca2+ influx more than two-fold compared with control in all three artery types, and hypoxia inhibited this increase by 74% in basilar, 49% in internal carotid, and 33% in common carotid arteries. Exposure to 10 microM serotonin and 100 microM uridine 5'-triphosphate (UTP) also increased Ca2+ influx, but these increases were less than observed during K+ contractions and averaged 10 (basilar), 31 (internal carotid), and 82% (common carotid) above control. Hypoxia completely inhibited serotonin- and/or UTP-induced increases in Ca2+ influx in basilar and internal carotid segments and inhibited 47% of this increase in the common carotid segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Bacterial meningitis in children: pathophysiology and treatment.

Recent studies of the pathophysiology of bacterial meningitis have suggested that the development of neuronal injury is related to the release of vasoactive substances or alteration of blood-brain barrier permeability. Cerebral edema, increased intracranial pressure (ICP), systemic hypotension, decreased cerebral perfusion pressure, vascular inflammation, thrombosis, and a variety of other vascular changes may result in global or regional reductions in cerebral blood flow (CBF), which contribute to this insult. Approximately one-third of infants and children with bacterial meningitis will have markedly reduced CBF, and even in those children with normal total flow, regional hypoperfusion is common. Reduced CBF is associated with cerebral edema and a poor prognosis. A poor prognosis also is associated with reduced cerebral perfusion pressure. This occurs early in the course of meningitis and is primarily due to increased ICP rather than systemic hypotension. Autoregulation is preserved, suggesting that local ischemic tissue injury is more related to factors such as regional edema formation, focal vascular pathology, or specific intrinsic flow/metabolic abnormalities than to a reduction in systemic blood pressure. In contrast with other acute CNS insults, CBF/PCO2 reactivity is well preserved in many patients with meningitis; this raises the possibility that hyperventilation may cause further ischemic injury in those patients with marginal CBF. Although it is still unclear that treatment of increased ICP will affect outcome, we propose a treatment paradigm based on the results of neuroimaging studies and ICP measurements.

Animals

Cerebral blood flow and carbon dioxide reactivity in children with bacterial meningitis.

We examined total and regional cerebral blood flow (CBF) by stable xenon computed tomography in 20 seriously ill children with acute bacterial meningitis to determine whether CBF was reduced and to examine the changes in CBF during hyperventilation. In 13 children, total CBF was normal (62 +/- 20 ml/min/100 gm) but marked local variability of flow was seen. In five other children, total CBF was significantly reduced (26 +/- 10 ml/min/100 gm; p less than 0.05), with flow reduced more in white matter (8 +/- 5 ml/min/100 gm) than in gray matter (30 +/- 15 ml/min/100 gm). Autoregulation of CBF appeared to be present in these 18 children within a range of mean arterial blood pressure from 56 to 102 mm Hg. In the remaining two infants, brain dead within the first 24 hours, total flow was uniformly absent, averaging 3 +/- 3 ml/min/100 gm. In seven children, CBF was determined at two carbon dioxide tension (PCO2) levels: 40 (+/- 3) mm Hg and 29 (+/- 3) mm Hg. In six children, total CBF decreased 33%, from 52 (+/- 25) to 35 (+/- 15) ml/min/100 gm; the mean percentage of change in CBF per millimeter of mercury of PCO2 was 3.0%. Regional variability of perfusion to changes in PCO2 was marked in all six children. The percentage of change in CBF per millimeter of mercury of PCO2 was similar in frontal gray matter (3.1%) but higher in white matter (4.5%). In the seventh patient a paradoxical response was observed; total and regional CBF increased 25% after hyperventilation. Our findings demonstrate that (1) CBF in children with bacterial meningitis may be substantially decreased globally, with even more variability noted regionally, (2) autoregulation of CBF is preserved, (3) CBF/CO2 responsitivity varies among patients and in different regions of the brain in the same patient, and (4) hyperventilation can reduce CBF below ischemic thresholds.

Bacterial Infections

Failure of electroencephalography to diagnose brain death in comatose children.

Two isoelectric electroencephalograms obtained 24 hours apart support a clinical diagnosis of brain death in prolonged coma. Without documentation of electrocerebral silence, physicians are reluctant to discontinue vital support systems. A radionuclide bolus technique has been developed that documents the absence of cerebral blood flow in suspected brain death and supplements the flat EEG. In a recent review of this technique, all 27 adults who had EEG activity maintained the integrity of their cerebral blood flow. This contrasts to our studies of 5 children, all of whom demonstrated persistent EEG activity but had no evidence of cerebral blood flow by either the isotope bolus technique (5 patients) or cerebral angiography (4 patients). These children (mean age, 7 months) lacked cephalic reflexes and were maintained on assisted ventilation for an average of 15 days. Multiple electroencephalographic tracings persistently demonstrated low-voltage cortical activity over this time. Despite the lack of cerebral blood flow, all patients were continued on respiratory support. At autopsy, extensive brain liquefaction necrosis was noted. In comatose children, EEG monitoring may be of limited value while cerebral blood flow measurements can provide more practical and prognostic information.

Brain Death

Radionuclide bolus angiography: a technique for verification of brain death in infants and children.

Fifteen infants and children, 11 of whom had clinical brain death and four of whom were comatose, were evaluated with the radionuclide bolus study and electroencephalography. Clinical criteria for brain death included: (1) absence of spontaneous respirations, (2) absence of cephalic reflexes, and (3) unresponsiveness. Results demonstrated complete correlation among clinical examination, EEG, and radionuclide study in 79% of cases. An approach to the evaluation of the infant or child with possible brain death is outlined utilizing serial examinations, radionuclide bolus study, and electroencephalography. The radionuclide bolus study appears to be a safe, rapid, portable technique which can be used for this purpose in infants and children.

Angiography

CBF and CBF/PCO2 reactivity in childhood strangulation.

Four children with self-inflicted strangulation injuries had cerebral blood flow determined by stable xenon computed tomography (XeCTCBF) within 24 hours of admission. All had suffered a severe hypoxic-ischemic cerebral injury; 3 initially had fixed pupils, all were apneic with varying bradyarrhythmias, and the initial mean arterial pH was 7.26 (+/- 0.18). The initial blood glucose values were greater than 300 mg/dl (334 and 351 mg/dl) in the 2 patients who died compared to the 2 who survived (104 and 295 mg/dl). The cardiac index was depressed during the first several days of hospitalization in the 2 patients who died (less than 2.0 L/min/m2) compared to the 2 who survived. Total CBF was normal (63 +/- 8 ml/min/100 gm) and local variations in CBF were present. PCO2 reactivity was determined by hyperventilating the 4 patients for 20 min from an end tidal PCO2 of 39 +/- 3 torr to 29 +/- 1 torr and then repeating the XeCTCBF study. Marked regional variability in the CBF/PCO2 response was observed, ranging from 0.5-5.5 ml/min/100 gm/torr PCO2. In the 2 patients who died, the CBF/PCO2 was decreased (1.2 ml/min/100 gm/torr PCO2) compared to the 2 patients who survived (2.1 ml/min/100 gm/torr PCO2). Although CBF was normal in these 4 children, the hyperventilation response was depressed, variable, and even paradoxical which may be important in the evolution of further brain injury and is a critical factor in deciding whether hyperventilation may be of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent